The DOI matches its Crossref record; 209 of the 209 references it cites were found in a registry or an index; none of the 253 sources its claims cite is checked for support yet.
The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders
Open accessAbstract
Perineuronal nets (PNN) are extracellular matrix (ECM) assemblies that preferentially ensheath parvalbumin (PV) expressing interneurons. Converging evidence indicates that PV cells and PNN are impaired in a variety of neurological disorders. PNN development and maintenance is necessary for a number of processes within the CNS, including regulation of GABAergic cell function, protection of neurons from oxidative stress, and closure of developmental critical period plasticity windows. Understanding PNN functions may be essential for characterizing the mechanisms of altered cortical excitability observed in neurodegenerative and neurodevelopmental disorders. Indeed, PNN abnormalities have been observed in post-mortem brain tissues of patients with schizophrenia and Alzheimer's disease. There is impaired development of PNNs and enhanced activity of its key regulator matrix metalloproteinase-9 (MMP-9) in Fragile X Syndrome, a common genetic cause of autism. MMP-9, a protease that cleaves ECM, is differentially regulated in a number of these disorders. Despite this, few studies have addressed the interactions between PNN expression, MMP-9 activity and neuronal excitability. In this review, we highlight the current evidence for PNN abnormalities in CNS disorders associated with altered network function and MMP-9 levels, emphasizing the need for future work targeting PNNs in pathophysiology and therapeutic treatment of neurological disorders.
Overview
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Written from the paper’s full text.
TL;DR
This review synthesizes evidence that perineuronal nets (PNNs) around parvalbumin (PV) interneurons are abnormal in multiple neurological disorders, often alongside dysregulated MMP-9. It proposes that MMP-9-mediated PNN cleavage contributes to impaired PV cell function and cortical hyperexcitability, highlighting PNN/MMP-9 pathways as potential therapeutic targets.
Key findings
- PNNs preferentially ensheath PV interneurons and are implicated in regulating GABAergic cell function, protecting neurons from oxidative stress, and closing developmental critical period plasticity; PNN abnormalities are reported in schizophrenia, Alzheimer’s disease, epilepsy, CNS injury/stroke, hearing loss, and Fragile X syndrome (FXS).
- In FXS, Fmr1 knockout mice show delayed PNN development and increased MMP-9 activity in developing auditory cortex, mostly between P14 and P21; genetic reduction of MMP-9 normalized PV/PNN development and reversed auditory cortical neuron hyperresponsiveness. FXS is reported to occur in 1 in 4000 males and 1 in 8000 females.
- In schizophrenia, post-mortem brains show reduced WFA-labeled PNN cells and reduced CSPGs and PV expression in prefrontal cortex; elevated plasma MMP-9 has been reported, and minocycline trials are cited as showing overall improvement in negative symptoms and executive functioning.
- In Alzheimer’s disease, post-mortem hippocampus shows reduced PNN expression; PNN-ensheathed cells were more resistant to Aβ1-42 and iron-induced oxidative stress. Table 1 reports that in adult sensory cortices a majority of PV cells express PNNs, e.g., visual cortex ∼70% at 3–5 months, somatosensory layer 4 young adult ∼80%, and auditory cortex CBA young adult 50%.
Methods
- Narrative review; no new experimental data are presented. It synthesizes published human post-mortem, rodent model, in vitro, EEG/electrophysiology, and clinical trial evidence.
- Includes Table 1 compiling studies of PV cells enwrapped by PNNs across visual, somatosensory, and auditory cortices, with mouse strain, staining methods, and percentages by age and layer where available.
- Main analysis is qualitative integration around a working hypothesis linking MMP-9 activity, PNN cleavage/reorganization, PV cell dysfunction, and altered network excitability.
Limitations
- Stated in the paper: the precise role of PNNs in network function and development is not known; future studies should compare intrinsic and synaptic properties of the same cell types with and without PNNs; chABC likely has broader effects, so genetic removal of specific PNN components is needed; PNNs are heterogeneous and composition may be brain-region- and age-specific; mechanisms of PNN loss and restructuring in disease remain unclear.
- Evident from the text: as a narrative review, there is no systematic search strategy or quantitative meta-analysis; causal direction between MMP-9, PNN changes, and excitability is often inferred from correlational animal and human data; therapeutic suggestions such as minocycline or MMP-9 inhibitors are based largely on preliminary or indirect evidence.
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Claims the paper makes
172 Not checked yet · 33 Own interpretation · 31 No basis given · 2 Own result
None of the sources cited for this claim have been checked yet.
In the paper
“Studies of postmortem human tissues also suggest developmental changes in lectican levels in human CNS.”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > PNN Structure and Developmental Regulation of its Components > Chondroitin Sulfate Proteoglycans
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In the paper
“In contrast, the expression of beta isoform increased 2–3 fold from embryonic day (E) 14 until birth and then decreased in adulthood.”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > PNN Structure and Developmental Regulation of its Components > Chondroitin Sulfate Proteoglycans
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In the paper
“In parallel, a number of these CNS diseases exhibit dysregulated expression of enzymes necessary for PNN cleavage and reorganization (Backstrom et al., 1996; Lorenzl et al., 2003; Rybakowski et al., 2009; Kim et al., 2009; Zhang et al., 2011; Yamamori et al., 2013; Liu et al., 2014; Rankin-Gee et al., 2015; Lepeta et al., 2017).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Introduction
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“There is impaired development of PNNs and enhanced activity of its key regulator matrix metalloproteinase-9 (MMP-9) in Fragile X Syndrome, a common genetic cause of autism.”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Abstract
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In the paper
“For example, high levels of brevican mRNA expression were detected in postmortem human cortex during early development until 8 years of age, and the expression levels were lower in the adult human brain (Gary et al., 2000).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > PNN Structure and Developmental Regulation of its Components > Chondroitin Sulfate Proteoglycans
What the sources say
- Not checked yetcites Gary et al., 2000 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Neurocan expression also increased between E14 and postnatal day (P) 3 and then decreased during early-late adolescence and into adulthood (Meyer-Puttlitz et al., 1996; Miller et al., 1996; Milev et al., 1998; Brückner et al., 2000).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > PNN Structure and Developmental Regulation of its Components > Chondroitin Sulfate Proteoglycans
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“MMP-9, a protease that cleaves ECM, is differentially regulated in a number of these disorders.”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Indeed, PNN abnormalities have been observed in post-mortem brain tissues of patients with schizophrenia and Alzheimer’s disease.”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“A developmental upregulation of aggrecan and brevican, which peak in adulthood, was reported in rat brain (Milev et al., 1998; Brückner et al., 2000; Popp et al., 2003).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > PNN Structure and Developmental Regulation of its Components > Chondroitin Sulfate Proteoglycans
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The expression of alpha isoform was low during embryonic development, first and second postnatal weeks, and then increased steadily until around 3.5 months of age (Bignami et al., 1993b).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > PNN Structure and Developmental Regulation of its Components > Chondroitin Sulfate Proteoglycans
What the sources say
- Not checked yetcites Bignami et al., 1993b
plaindirect- Asserted: passes — The authors put it forward as true.
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- Probably not a substantial claim. 44
- It may state two separate claims as one. 55
In the paper
“By week 4, tenascin expression is reduced to adult levels (Brückner et al., 2000).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > PNN Structure and Developmental Regulation of its Components > Tenascins and Hyaluronan
What the sources say
- Not checked yetcites Brückner et al., 2000 source
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“In the mouse cortex, tenascin immunolabeling is first detected around E16 (Sheppard et al., 1991) and tenascin levels increase after birth until the third postnatal week (Brückner et al., 2000).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > PNN Structure and Developmental Regulation of its Components > Tenascins and Hyaluronan
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
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In the paper
“Similar to lecticans, tenascin and hyaluronan are also developmentally regulated.”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > PNN Structure and Developmental Regulation of its Components > Tenascins and Hyaluronan
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Peak MMP-9 expression is observed during postnatal development and is reduced during adulthood (Bednarek et al., 2009; Reinhard et al., 2015; Wen et al., 2017).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Parvalbumin Expressing Interneurons, PNNs and MMP-9
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“While lecticans, tenascins, and hyaluronan are expressed during embryonic development, the classic net-like structure of PNNs is not typically seen until later during postnatal development.”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > PNN Structure and Developmental Regulation of its Components > Tenascins and Hyaluronan
hedged- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
In the paper
“Hyaluronan is expressed during postnatal development and adulthood but peaks during embryonic development (Bignami et al., 1993a).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > PNN Structure and Developmental Regulation of its Components > Tenascins and Hyaluronan
What the sources say
- Not checked yetcites Bignami et al., 1993a
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Interestingly, developing auditory cortex appears to exhibit fewer PNN and PV expressing cells than visual or somatosensory cortex, but in adult sensory cortices, a majority of PV cells express PNNs as seen with WFA staining.”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Parvalbumin Expressing Interneurons, PNNs and MMP-9
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“Auditory hypersensitivity is also evident in Fmr1 knockout (KO) mice, a mouse model of FXS, which exhibit increased susceptibility to audiogenic seizures (Musumeci et al., 2000) and abnormal auditory startle (Frankland et al., 2004).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Fragile X Syndrome
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
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In the paper
“Hyaluronan expression precedes the detection of both tenascin and lecticans, and is first observed near the notochord in E11-12 rat embryos (Delpech and Delpech, 1984; Bignami et al., 1993a).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > PNN Structure and Developmental Regulation of its Components > Tenascins and Hyaluronan
What the sources say
- Not checked yetcites Delpech and Delpech, 1984
- Not checked yetcites Bignami et al., 1993a
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“In this study, monocular deprivation followed by light exposure in adult mice was associated with reduced WFA-expressing PNNs, lower aggrecan levels, and increased MMP-9 activity, as well as reduced PV cell output, increased firing of regular-spiking cells, and reduced gamma power (Murase et al., 2017).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Parvalbumin Expressing Interneurons, PNNs and MMP-9
What the sources say
- Not checked yetcites Murase et al., 2017 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“A large proportion of PNN-expressing PV cells is found within layer 4 of neocortex (Table 1).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Parvalbumin Expressing Interneurons, PNNs and MMP-9
What the sources say
- Not checked yetcites Table 1
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Studies of rodent visual cortex development indicate that Otx2 is localized to GABAergic cells, and is more likely found in PV cells that are enwrapped with PNNs, which contain a specific Otx2 binding site (Beurdeley et al., 2012).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Fragile X Syndrome
What the sources say
- Not checked yetcites Beurdeley et al., 2012 source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These phenotypes were mostly observed between P14 and P21 suggesting a window of abnormal development that can be targeted for therapeutic applications.”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Fragile X Syndrome
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“RNA sequencing analysis of PV cells containing Otx2 indicates that Otx2 may be necessary for mitochondrial function, cellular respiration, and redox regulation (Sakai et al., 2017).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Fragile X Syndrome
What the sources say
- Not checked yetcites Sakai et al., 2017 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“There is also enhanced N1 amplitude and reduced gamma phase locking in auditory ERPs (Lovelace et al., 2018).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Fragile X Syndrome
What the sources say
- Not checked yetcites Lovelace et al., 2018 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At P14, the responses of single neurons were similar across genotypes, while at P21, Fmr1 KO neurons show hyper-responsiveness.”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Fragile X Syndrome
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Genetic reduction of MMP-9 levels in the Fmr1 KO mice normalized PV/PNN development and also reversed the hyperresponsiveness of auditory cortical neurons.”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Fragile X Syndrome
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Redox dysregulation has been observed in schizophrenic patients, who have defective antioxidant systems and exhibit increased lipid peroxidation (Do et al., 2000; Yao et al., 2006; Flatow et al., 2013).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Schizophrenia
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Post-mortem brains from patients with schizophrenia exhibit reduced density of WFA-labeled cells (Mauney et al., 2013) and reduced levels of CSPGs and PV expression in prefrontal cortex (Enwright et al., 2016).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Schizophrenia
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In contrast, gamma-band activity that is driven by rapid presentation of auditory stimuli and synchrony or phase-locking of electrocortical activity to these stimuli are reduced in schizophrenic patients compared to healthy controls (Kwon et al., 1999; Light et al., 2006).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Schizophrenia
What the sources say
- Not checked yetcites Kwon et al., 1999
- Not checked yetcites Light et al., 2006
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“While this mechanism has not been confirmed, chABC-mediated removal of chondroitin sulfate side chains from PNNs reduced spiking of PV cells in adult rats (Balmer, 2016; Lensjø et al., 2017) and increased spiking variability (Lensjø et al., 2017).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Schizophrenia
What the sources say
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Analysis of molecular mechanisms indicates that chondroitin sulfate promotes activation of protein kinase pathways including PKC and PI3K/Akt, and subsequent production of a neuronal antioxidant, heme oxygenase-1 (Cañas et al., 2007).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Schizophrenia
What the sources say
- Not checked yetcites Cañas et al., 2007
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Drug-induced seizures led to increased expression of aggrecan cleavage products around PV cells and reduced expression of PNN components in rodent hippocampus, including Ctrl1 and hyaluronan synthase 3, both of which help to stabilize PNNs (McRae and Porter, 2012; Rankin-Gee et al., 2015).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Seizures and Epilepsy
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Tenascins are fibrous, matricellular proteins, which bind to the C-terminal domain of lecticans (Aspberg et al., 1997; Day et al., 2004).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > PNN Structure and Developmental Regulation of its Components > Tenascins and Hyaluronan
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“PNNs are composed of CSPGs, tenascin, and link proteins, which facilitate binding to a hyaluronan backbone (Yamaguchi, 1999) (Figure 2).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > PNN Structure and Developmental Regulation of its Components
What the sources say
- Not checked yetcites Yamaguchi, 1999 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Versican consists of two different alpha and beta isoforms, which are differentially expressed during development.”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > PNN Structure and Developmental Regulation of its Components > Chondroitin Sulfate Proteoglycans
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Perineuronal nets are specialized assemblies of ECM proteins which ensheath neurons and proximal dendrites (Celio et al., 1998).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > PNN Structure and Developmental Regulation of its Components
What the sources say
- Not checked yetcites Celio et al., 1998 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Chondroitin sulfate proteoglycans consist of a core protein and varying amounts of chondroitin sulfate chains covalently bound to a central region of the protein.”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > PNN Structure and Developmental Regulation of its Components > Chondroitin Sulfate Proteoglycans
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Since then, PNNs have been implicated in a wide range of functions including neuroprotection, regulation of neural activity and experience-dependent plasticity.”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Introduction
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“MMP-9, a protease that cleaves ECM, is differentially regulated in a number of these disorders.”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“These include aggrecan, neurocan, versican, and brevican, which vary in core protein size and the number of GAG side chains (Yamaguchi, 1999).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > PNN Structure and Developmental Regulation of its Components > Chondroitin Sulfate Proteoglycans
What the sources say
- Not checked yetcites Yamaguchi, 1999 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we propose a novel working hypothesis in which MMP-9 mediated cleavage and/or reorganization of PNN structures around PV-expressing cells contributes to abnormal PV cell development and cortical hyperexcitability (Figure 1).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Introduction
hedgedconditional- Asserted: fails — The authors may not put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The authors may not put it forward as true. The paper may give no reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Since then, PNNs have been implicated in a wide range of functions including neuroprotection, regulation of neural activity and experience-dependent plasticity.”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Introduction
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“However, the functional impact of developmental changes in PNN lectican composition is unknown.”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > PNN Structure and Developmental Regulation of its Components > Chondroitin Sulfate Proteoglycans
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Despite this, few studies have addressed the interactions between PNN expression, MMP-9 activity and neuronal excitability.”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
In the paper
“Hyaluronan is an unsulfated GAG that is synthesized at the cell surface by the membrane-bound enzymes called HAS and protrudes through the plasma membrane into the extracellular space (Fraser et al., 1997).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > PNN Structure and Developmental Regulation of its Components > Tenascins and Hyaluronan
What the sources say
- Not checked yetcites Fraser et al., 1997 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“These chondroitin sulfate side chains are a type of GAG polysaccharide consisting of disaccharide blocks of N-acetylgalactosamine and glucuronic acid (Sherman and Back, 2007).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > PNN Structure and Developmental Regulation of its Components > Chondroitin Sulfate Proteoglycans
What the sources say
- Not checked yetcites Sherman and Back, 2007 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“However, the role of PNNs in neural and network excitability is only beginning to be understood (Balmer, 2016; Murase et al., 2017; Wen et al., 2017).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Introduction
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Although lecticans are developmentally regulated, their function in CNS development remains unclear.”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > PNN Structure and Developmental Regulation of its Components > Chondroitin Sulfate Proteoglycans
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Various CSPGs exist in the ECM throughout the body, but the lectican family of CSPGs is most prominent in PNNs of the CNS.”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > PNN Structure and Developmental Regulation of its Components > Chondroitin Sulfate Proteoglycans
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we bring together evidence from studies of schizophrenia, AD, and epilepsy to suggest that systematic studies of the interplay between MMP-9, PNN and PV cells may be key to understanding mechanisms of multiple CNS disorders at the cellular and circuit levels.”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Introduction
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
In the paper
“FXS is a leading genetic cause of autism, occurring in 1 in 4000 males and 1 in 8000 females (Murray et al., 1997).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Fragile X Syndrome
What the sources say
- Not checked yetcites Murray et al., 1997 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Parvalbumin cells are a major class of GABAergic, fast-spiking inhibitory interneurons in the neocortex.”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Parvalbumin Expressing Interneurons, PNNs and MMP-9
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“It is unclear how these molecules are assembled to form PNN around neurons, but some studies suggest that both neurons and glial cells are involved in the process (Miyata et al., 2007; Pyka et al., 2011).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > PNN Structure and Developmental Regulation of its Components > Tenascins and Hyaluronan
What the sources say
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“As aggrecan has been previously identified as an MMP-9 target (Mercuri et al., 2000; Madsen et al., 2010; Rankin-Gee et al., 2015), aggrecan-rich PNNs may be unstable in the presence of MMP-9, leading to abnormal development and neural excitability (Murase et al., 2017; Wen et al., 2017).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Parvalbumin Expressing Interneurons, PNNs and MMP-9
What the sources say
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“This leads to loss of Fragile X Mental Retardation protein (FMRP), which is necessary for regulation of protein synthesis (Verkerk et al., 1991).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Fragile X Syndrome
What the sources say
- Not checked yetcites Verkerk et al., 1991 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The most common cause of FXS is an expansion of CGG trinucleotide repeats in 5′ region of the Fragile X mental retardation 1 (Fmr1) gene that results in its hypermethylation and inactivation.”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Fragile X Syndrome
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Astrocytes extend their processes into PNNs localized near the synapse (Brückner et al., 1993; Blümcke et al., 1995), suggesting a tetrapartite synaptic organization involving ECM, pre/post synaptic sites and astrocytes (Dityatev and Rusakov, 2011; Smith et al., 2015) whose synergistic functions remain unexplored.”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > PNN Structure and Developmental Regulation of its Components > Tenascins and Hyaluronan
What the sources say
- Not checked yetcites Dityatev and Rusakov, 2011
- Not checked yetcites Smith et al., 2015 source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“It is unclear how these molecules are assembled to form PNN around neurons, but some studies suggest that both neurons and glial cells are involved in the process (Miyata et al., 2007; Pyka et al., 2011).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > PNN Structure and Developmental Regulation of its Components > Tenascins and Hyaluronan
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Individuals with this neurodevelopmental disorder suffer from social and communication deficits, sensory hypersensitivity, and anxiety disorders (Abbeduto and Hagerman, 1997; Rogers et al., 2001).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Fragile X Syndrome
What the sources say
- Not checked yetcites Abbeduto and Hagerman, 1997
- Not checked yetcites Rogers et al., 2001
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Like PNNs, PV expression is developmentally regulated and experience-dependent (Hensch, 2005).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Parvalbumin Expressing Interneurons, PNNs and MMP-9
What the sources say
- Not checked yetcites Hensch, 2005 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“MMP-9 is a zinc-dependent endopeptidase expressed in various cells within the CNS which is capable of cleaving ECM proteins, including collagen and laminin (reviewed in Reinhard et al., 2015).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Parvalbumin Expressing Interneurons, PNNs and MMP-9
What the sources say
- Not checked yetcites Reinhard et al., 2015 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“One mechanism that has been proposed to explain some symptoms of schizophrenia is a reduction in GABAergic signaling in specific cortical regions.”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Schizophrenia
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We found delayed PNN development and increased MMP-9 activity levels in the developing auditory cortex of Fmr1 KO mice (Wen et al., 2017), which may lead to impaired PV cell development and reduced inhibition.”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Fragile X Syndrome
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“This suggests that during development, sensory stimuli can activate Narp expression which promotes PV interneuron excitation, leading to feed-forward inhibition (O’Brien et al., 1999; Gu et al., 2013).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Fragile X Syndrome
What the sources say
- Not checked yetcites O’Brien et al., 1999 source
- Not checked yetcites Gu et al., 2013
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“An orthodenticle homeoprotein, Otx2, may play a role in PV cell maturation and refinement of cortical inhibition.”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Fragile X Syndrome
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These results indicate that there is altered E/I balance in auditory cortex, which may underlie auditory hypersensitivity phenotypes.”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Fragile X Syndrome
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In FXS, delayed development of PNNs may contribute to abnormal Narp expression, impairing the ability of PV cells to scale cortical networks, resulting in cortical hyperexcitability.”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Fragile X Syndrome
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Perineuronal net dysfunction in schizophrenia may also drive changes in GABAergic cell function leading to network dysfunction, as normal PNN expression regulates excitability of PV cells (Liu et al., 2013; Balmer, 2016).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Schizophrenia
What the sources say
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Recent studies show that PNNs may protect PV cells from oxidative stress (Cabungcal et al., 2013; Morishita et al., 2015), and thus serve as a ‘safety net’ to support the rapid firing properties of PV cells.”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Schizophrenia
What the sources say
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Scn1a is a gene that encodes Nav1.1, a sodium channel necessary for PV cell firing (Ogiwara et al., 2007; Hedrich et al., 2014).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Seizures and Epilepsy
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Beside its antibiotic activity, minocycline can reduce plasma levels of MMP-9 (Dziembowska et al., 2013) and inhibit MMP-9 activity (Lee et al., 2006), suggesting a possible role of MMP-9 inhibition in the beneficial effects of minocycline in schizophrenia.”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Schizophrenia
What the sources say
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“which lead to denervation of upstream pathways and inactivation of parts of somatosensory cortex (Davies et al., 1999; Kaas et al., 2008).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > CNS Injury and Stroke
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The molecules can react with free radicals generated by cellular metabolism to generate even more free radicals, resulting in lipid peroxidation, oxidative stress, and cell death (Stohs and Bagchi, 1995).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Alzheimer’S Disease
What the sources say
- Not checked yetcites Stohs and Bagchi, 1995 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“CSPG immunoreactivity is down regulated although they remain detectable up to 14 days post-injury (Hobohm et al., 2005).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > CNS Injury and Stroke
What the sources say
- Not checked yetcites Hobohm et al., 2005 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“reduced PV-immunoreactivity and PV cell function have also been observed following stroke”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > CNS Injury and Stroke
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“This may lead to hippocampal and cortical hyperexcitability as well as increased seizure susceptibility in both AD humans and rodent models (Palop et al., 2007; Roberson et al., 2011).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Alzheimer’S Disease
What the sources say
- Not checked yetcites Palop et al., 2007 source
- Not checked yetcites Roberson et al., 2011
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“As PNNs regulate PV cell activity (Balmer, 2016; Lensjø et al., 2017) and protect PV cells from oxidative stress (Cabungcal et al., 2013), PNNs can be potentially targeted to control seizures.”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Seizures and Epilepsy
What the sources say
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
In the paper
“The number of PNN expressing cells is reduced in aging mouse auditory cortex with a particular impact on PV/PNN co-localized cells (Brewton et al., 2016).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Hearing Loss and Central Auditory Processing
What the sources say
- Not checked yetcites Brewton et al., 2016 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Overexposure to loud sounds can cause hair cell damage (Puel et al., 1998)”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Hearing Loss and Central Auditory Processing
What the sources say
- Not checked yetcites Puel et al., 1998 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Recent studies indicate that minocycline administration may reverse both schizophrenia and FXS phenotypes, perhaps due to its ability to lower MMP-9 levels or activity (Dziembowska et al., 2013).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Conclusion and Future Studies
What the sources say
- Not checked yetcites Dziembowska et al., 2013 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“GABAergic signaling is involved in shaping these properties, with fast-spiking PV cells shaping both spectral and temporal selectivity (Moore and Wehr, 2012).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Hearing Loss and Central Auditory Processing
What the sources say
- Not checked yetcites Moore and Wehr, 2012 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“activity-dependent synaptogenesis and the development of stable neuronal networks may be a result of normal PNN interactions with inhibitory interneurons, in particular fast spiking PV cells.”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Conclusion and Future Studies
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“PNNs are also implicated in experience-dependent plasticity during development.”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Conclusion and Future Studies
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“Age-related hearing loss, also known as presbycusis, is associated with difficulty interpreting speech and slower auditory processing (Gates and Mills, 2005)”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Hearing Loss and Central Auditory Processing
What the sources say
- Not checked yetcites Gates and Mills, 2005
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Altered PNN formation may contribute to abnormal GABAergic signaling and impaired temporal processing with age, leading to deficits in speech comprehension.”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Hearing Loss and Central Auditory Processing
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“While the use of chABC has been useful in addressing PNN function, this enzyme likely has broader effects.”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Conclusion and Future Studies
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
In the paper
“hearing loss and reduced afferent input in the auditory system (Syka, 2002).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Hearing Loss and Central Auditory Processing
What the sources say
- Not checked yetcites Syka, 2002 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“in the rodent hippocampus, aggrecan-expressing PNNs overlap with WFA labeling in stratum oriens, but stratum pyramidale exhibits aggrecan-rich PNNs, which are not WFA-positive (Yamada and Jinno, 2017).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Conclusion and Future Studies
What the sources say
- Not checked yetcites Yamada and Jinno, 2017
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“While iron-induced oxidative stress resulted in apoptotic cell death in cells without PNNs, neurons with PNNs were more likely to survive (Suttkus et al., 2012, 2014).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Alzheimer’S Disease
What the sources say
- Not checked yetcites Suttkus et al., 2012, 2014
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“elevated MMP-9 levels may contribute to both PNN degradation and altered levels of Aβ in AD.”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Alzheimer’S Disease
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: MMP-9 is involved in PNN maintenance.
In the paper
“Tenascin-R expressing PNNs are not observed in rodent PFC, but are prominent in other cortical areas (Ueno et al., 2017a).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Conclusion and Future Studies
What the sources say
- Not checked yetcites Ueno et al., 2017a
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“and may be indicators for risk of stroke mortality (Hansson et al., 2011).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Conclusion and Future Studies
What the sources say
- Not checked yetcites Hansson et al., 2011 source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“TIMP levels are increased in postmortem brains of AD patients (Peress et al., 1995)”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Conclusion and Future Studies
What the sources say
- Not checked yetcites Peress et al., 1995 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the ADAMTs family of aggrecanases may also cause PNN cleavage and reorganization.”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Conclusion and Future Studies
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“this may allow for axonal outgrowth and synaptogenesis, particularly in surviving cortical areas, which exhibit reduced CSPG and PNN expression and are therefore growth permissive (2014).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Conclusion and Future Studies
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“tissue inhibitors of MMPs, known as TIMPs, which form 1:1 complexes with MMPs in order to inhibit MMP activity (Gomis-Rüth et al., 1997; Brew and Nagase, 2010).”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Conclusion and Future Studies
What the sources say
- Not checked yetcites Gomis-Rüth et al., 1997 source
- Not checked yetcites Brew and Nagase, 2010
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“these may be crucial in understanding MMP-9 dysregulation in CNS disorders”
§ The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders > Conclusion and Future Studies
What the sources say
- Not checked yetcites Papa et al., 2014 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
The paper relies on this without support.
Re-establishing neuronal plasticity is key for re-innervation and recovery after CNS injury and stroke.
“In CNS injury and stroke, re-establishing neuronal plasticity appears to be key for re-innervation and recovery.”
The paper relies on this without support.
MMP-9 is involved in PNN maintenance.
“As MMP-9 is also involved in PNN maintenance”
The paper relies on this without support.
Neurotrophins are necessary for neuronal growth and plasticity.
“Neurotrophins are necessary for neuronal growth and plasticity”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“Importantly, PNN regulate the synaptic plasticity (Kochlamazashvili et al., 2010) and rewiring the network (Pollock et al., 2014) of the interneurons (Wen et al., 2018).”
From Disrupted structural connectivity in ArcAβ mouse model of Aβ amyloidosis (2020) · cites this paper as Wen et al., 2018
In the citing paper
“microglia undergo activation and subsequently release matrix metalloproteinases (e.g. MMP9) or other ECM-degrading proteases that act on PNN components [33].”
From Microglia facilitate loss of perineuronal nets in the Alzheimer's disease brain (2020) · cites this paper as [33]
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“Importantly, PNN regulate the synaptic plasticity (Kochlamazashvili et al., 2010) and rewiring the network (Pollock et al., 2014) of the interneurons (Wen et al., 2018).”
Background
Metadata
- Authors
- Wen, T. H., Binder, D. K., Ethell, I. M., & Razak, K. A.
- Affiliations
- University of California, Riverside (US)
- Corresponding author
- Ethell, Iryna M.
- Razak, Khaleel A.
- Venue
- Frontiers in Molecular Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2018-08-03
- Volume
- 11
- Pages
- 270-270
- ISSN
- 1662-5099 (ISSN-L)
- PMC
- PMC6085424
- OpenAlex
- W2886787141
- Cited by
- 170
- References
- 209
- Citations by year
- 2026: 15 · 2025: 21 · 2024: 16 · 2023: 26 · 2022: 27 · 2021: 27 · 2020: 24 · 2019: 12 · 2018: 2
- FWCI
- 2.10
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Frontiers in Molecular Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- National Institutes of Health (U54 HD082008)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Keywords
- perineuronal nets, extracellular matrix, parvalbumin interneurons, MMP-9, fragile X syndrome, autism spectrum disorder, schizophrenia, Alzheimer's disease, cortical excitability, critical period plasticity, GABAergic inhibition, oxidative stress, neurodevelopmental disorders, neurodegenerative diseases
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