Cited by 170Neuroscience and Neuropharmacology ResearchGenetics and Neurodevelopmental DisordersProtease and Inhibitor Mechanisms

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 access

Wen, Teresa H., Binder, Devin K., Ethell, Iryna M., Razak, Khaleel A.·2018·Frontiers in Molecular Neuroscience

DOI 10.3389/fnmol.2018.00270PMC PMC6085424

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Abstract

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.

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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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Integrity signals

Registry

Crossref · 10.3389/fnmol.2018.00270

Cites

209 of 209 references verified0 citation errors · 0 not checkable

Statistics

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Claims the paper makes

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None of the sources cited for this claim have been checked yet.
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
- Not checked yetcites Backstrom et al., 1996 source
- Not checked yetcites Lorenzl et al., 2003 source
- Not checked yetcites Rybakowski et al., 2009 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
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
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
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
- Not checked yetcites Meyer-Puttlitz et al., 1996 source
- Not checked yetcites Miller et al., 1996 source
- Not checked yetcites Milev et al., 1998 source
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
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
- Not checked yetcites Milev et al., 1998 source
- Not checked yetcites Brückner et al., 2000 source
- Not checked yetcites Popp et al., 2003 source
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
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
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes

Show all 150 claims

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
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
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
“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
- Not checked yetcites Sheppard et al., 1991 source
- Not checked yetcites Brückner et al., 2000 source
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
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
- Not checked yetcites Bednarek et al., 2009 source
- Not checked yetcites Reinhard et al., 2015 source
- Not checked yetcites Wen et al., 2017 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
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
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
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
- Not checked yetcites Musumeci et al., 2000 source
- Not checked yetcites Frankland et al., 2004 source
Load-bearingStrength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
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
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
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
Load-bearingStrength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
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
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
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
Load-bearingStrength:hedged· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
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
Strength:hedged· not yet calibratedCausal:conditional· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
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
Load-bearingStrength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
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
- Not checked yetcites Do et al., 2000
- Not checked yetcites Yao et al., 2006 source
- Not checked yetcites Flatow et al., 2013 source
Load-bearingStrength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
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
- Not checked yetcites Mauney et al., 2013 source
- Not checked yetcites Enwright et al., 2016 source
Load-bearingStrength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
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
Load-bearingStrength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
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
- Not checked yetcites Balmer, 2016 source
- Not checked yetcites Lensjø et al., 2017 source
Load-bearingStrength:hedged· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
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
Load-bearingStrength:hedged· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
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
- Not checked yetcites Aspberg et al., 1997 source
- Not checked yetcites Day et al., 2004 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
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
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
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
Load-bearingStrength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
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
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
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
“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
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
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
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
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
- Not checked yetcites Balmer, 2016 source
- Not checked yetcites Murase et al., 2017 source
- Not checked yetcites Wen et al., 2017 source
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✗ Checkable: fails✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
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
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
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
- Not checked yetcites Miyata et al., 2007 source
- Not checked yetcites Pyka et al., 2011 source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
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
- Not checked yetcites Murase et al., 2017 source
- Not checked yetcites Wen et al., 2017 source
Load-bearingStrength:hedged· not yet calibratedCausal:conditional· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
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
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
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
Strength:hedged· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
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
- Not checked yetcites Miyata et al., 2007 source
- Not checked yetcites Pyka et al., 2011 source
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
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
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
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
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
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
Load-bearingStrength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
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
Load-bearingStrength:hedged· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
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
- Not checked yetcites Liu et al., 2013 source
- Not checked yetcites Balmer, 2016 source
Load-bearingStrength:hedged· not yet calibratedCausal:conditional· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
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
- Not checked yetcites Cabungcal et al., 2013 source
- Not checked yetcites Morishita et al., 2015 source
Load-bearingStrength:hedged· not yet calibratedCausal:conditional· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
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
- Not checked yetcites Ogiwara et al., 2007 source
- Not checked yetcites Hedrich et al., 2014 source
Load-bearingStrength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
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
- Not checked yetcites Dziembowska et al., 2013 source
- Not checked yetcites Lee et al., 2006 source
Load-bearingStrength:hedged· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
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
- Not checked yetcites Davies et al., 1999 source
- Not checked yetcites Kaas et al., 2008 source
Load-bearingStrength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
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
Load-bearingStrength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
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
Load-bearingStrength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
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
- Not checked yetcites Hobohm et al., 2005 source
- Not checked yetcites Xie et al., 2014 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
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
Strength:hedged· not yet calibratedCausal:conditional· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
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
- Not checked yetcites Balmer, 2016 source
- Not checked yetcites Lensjø et al., 2017 source
- Not checked yetcites Cabungcal et al., 2013 source
Load-bearingStrength:hedged· not yet calibratedCausal:conditional· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
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
Load-bearingStrength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
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
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
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
Load-bearingStrength:hedged· not yet calibratedCausal:conditional· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
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
Load-bearingStrength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
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
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
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
Load-bearingStrength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
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
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
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
Load-bearingStrength:hedged· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
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
Load-bearingStrength:hedged· not yet calibratedCausal:conditional· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
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
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
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
Strength:hedged· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
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
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
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
“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
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
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
Load-bearingStrength:hedged· not yet calibratedCausal:conditional· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
Probably not a substantial claim.

88 of 88

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”

3 of 3

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?

Items 201–209 of 209

Genome-Wide Target Analyses of Otx2 Homeoprotein in Postnatal Cortex
Sakai, A., Nakato, R., Ling, Y., Hou, X., Hara, N., Iijima, T., Yanagawa, Y., Kuwano, R., Okuda, S., Shirahige, K., et al. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00307 · Cited by 30
Aggrecanase- and matrix metalloproteinase-mediated aggrecan degradation is associated with different molecular characteristics of aggrecan and separated in time ex vivo
Madsen, S. H., Sumer, E. U., Bay-Jensen, A.-C., Sondergaard, B.-C., Qvist, P., & Karsdal, M. A. (2010) · Biomarkers · doi:10.3109/13547500903521810 · Cited by 29
Modulation of matrix metalloproteinases activity in the ventral horn of the spinal cord re-stores neuroglial synaptic homeostasis and neurotrophic support following peripheral nerve injury.
Cirillo, G., Colangelo, A. M., De Luca, C., Savarese, L., Barillari, M. R., Alberghina, L., & Papa, M. (2016) · PLoS ONE · doi:10.1371/journal.pone.0152750 · Cited by 27
Blood assessment of the expression levels of matrix metalloproteinase 9 (MMP9) and its natural inhibitor, TIMP1 genes in Iranian schizophrenic patients.
Rahimi, S., Sayad, A., Moslemi, E., Ghafouri-Fard, S., & Taheri, M. (2017) · Metabolic Brain Disease · doi:10.1007/s11011-017-0043-z · Cited by 24
Perineuronal nets increase inhibitory GABAergic currents during the critical period in rats.
Liu (2013) · PubMed · doi:10.3980/j.issn.2222-3959.2013.02.02 · Cited by 23
Altered cortical spectrotemporal processing with age-related hearing loss
Trujillo, M. S., & Razak, K. A. (2013) · Journal of Neurophysiology · doi:10.1152/jn.00423.2013 · Cited by 21
Self-citation
Abolished perineuronal nets and altered parvalbumin-immunoreactivity in the nucleus reticularis thalami of wildtype and 3xTg mice after experimental stroke
Härtig, W., Appel, S., Suttkus, A., Grosche, J., & Michalski, D. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2016.09.004 · Cited by 15
Untitled work
Meyer-Puttlitz (1996) · doi:10.1002/(sici)1096-9861(19960226)366:1
Postnatal development of perineuronal nets in wild-type mice and in a mutant deficient in tenascin-R
Br�ckner, G., Grosche, J., Schmidt, S., H�rtig, W., Margolis, R. U., Delpech, B., Seidenbecher, C. I., Czaniera, R., & Schachner, M. (2000) · The Journal of Comparative Neurology · doi:10.1002/1096-9861(20001225)428:4

Flagged first, then by citations

Research works printed but not linked: 5

Berardi, 2004, Extracellular matrix and visual cortical plasticity: freeing the synapse., Neuron, 44, 905, 10.1016/j.neuron.2004.12.008 · DOI
Golgi, 1893, Intorno all’origine del quarto nervo cerebrale e una questione istofisiologica che a questo argomento si collega., Rend. R Accademia Lincei, 2, 378
Mercuri, 2000, Mutations in the interglobular domain of aggrecan alter matrix metalloproteinase and aggrecanase cleavage patterns. Evidence that matrix metalloproteinase cleavage interferes with aggrecanase activity., J. Biol. Chem., 275, 33038, 10.1074/jbc.275.42.33038 · DOI · Paper page
Ramón, 1897, Las células de cilindro-eje corto de la capa molecular del cerebro., Rev. Trim Micrográf., 2, 105
Volk, 2000, Decreased GAD67 mRNA expression in a subset of prefrontal cortical GABA neurons in subjects with schizophrenia., Arch. Gen. Psychiatry, 57, 237, 10.1001/archpsyc.57.3.237 · DOI · Paper page

Sorted by citations

Microglia facilitate loss of perineuronal nets in the Alzheimer's disease brain
Crapser, J. D., Spangenberg, E. E., Barahona, R. A., Arreola, M. A., Hohsfield, L. A., & Green, K. N. (2020) · EBioMedicine · doi:10.1016/j.ebiom.2020.102919 · Cited by 280
MMPs in learning and memory and neuropsychiatric disorders
Beroun, A., Mitra, S., Michaluk, P., Pijet, B., Stefaniuk, M., & Kaczmarek, L. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03180-8 · Cited by 207
Decreased Density of Perineuronal Net in Prelimbic Cortex Is Linked to Depressive-Like Behavior in Young-Aged Rats
Yu, Z., Chen, N., Hu, D., Chen, W., Yuan, Y., Meng, S., Zhang, W., Lu, L., Han, Y., & Shi, J. (2020) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2020.00004 · Cited by 52
Effects of developmental noise exposure on inhibitory cell densities and perineuronal nets in A1 and AAF of mice
Reinhard, S. M., Abundez-Toledo, M., Espinoza, K., & Razak, K. A. (2019) · Hearing Research · doi:10.1016/j.heares.2019.107781 · Cited by 15
Self-citation
Disrupted structural connectivity in ArcAβ mouse model of Aβ amyloidosis
Al-Amin, M. M., Grandjean, J., Klohs, J., & Kim, J. (2020) · doi:10.1101/2020.04.27.064634 · Cited by 2
“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

See all 170

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.
ORCID: Wen, Teresa H.
Binder, Devin K.
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)
DOI: 10.3389/fnmol.2018.00270
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
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (unspecified)
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

A language model drew the claims from the paper on 2026-10-06, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).

A second model labelled each claim on 2026-10-06 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders

Abstract

Overview

AI snapshot

TL;DR

Key findings

Methods

Limitations

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Metadata

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About these checks