The DOI matches its Crossref record; 186 of the 189 references it cites were found in a registry or an index; none of the 159 sources its claims cite is checked for support yet.
Losing the sugar coating: Potential impact of perineuronal net abnormalities on interneurons in schizophrenia
Open accessAbstract
Perineuronal nets (PNNs) were shown to be markedly altered in subjects with schizophrenia. In particular, decreases of PNNs have been detected in the amygdala, entorhinal cortex and prefrontal cortex. The formation of these specialized extracellular matrix (ECM) aggregates during postnatal development, their functions, and association with distinct populations of GABAergic interneurons, bear great relevance to the pathophysiology of schizophrenia. PNNs gradually mature in an experience-dependent manner during late stages of postnatal development, overlapping with the prodromal period/age of onset of schizophrenia. Throughout adulthood, PNNs regulate neuronal properties, including synaptic remodeling, cell membrane compartmentalization and subsequent regulation of glutamate receptors and calcium channels, and susceptibility to oxidative stress. With the present paper, we discuss evidence for PNN abnormalities in schizophrenia, the potential functional impact of such abnormalities on inhibitory circuits and, in turn, cognitive and emotion processing. We integrate these considerations with results from recent genetic studies showing genetic susceptibility for schizophrenia associated with genes encoding for PNN components, matrix-regulating molecules and immune system factors. Notably, the composition of PNNs is regulated dynamically in response to factors such as fear, reward, stress, and immune response. This regulation occurs through families of matrix metalloproteinases that cleave ECM components, altering their functions and affecting plasticity. Several metalloproteinases have been proposed as vulnerability factors for schizophrenia. We speculate that the physiological process of PNN remodeling may be disrupted in schizophrenia as a result of interactions between matrix remodeling processes and immune system dysregulation. In turn, these mechanisms may contribute to the dysfunction of GABAergic neurons.
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“Our group has shown marked decreases of PNNs in several brain regions of subjects diagnosed with SZ (Mauney et al., 2013; Pantazopolous et al., 2014; Pantazopoulos et al., 2010).”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > 2. PERINEURONAL NET ABNORMALITIES IN SCHIZOPHRENIA
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In the paper
“In particular, decreases of PNNs have been detected in the amygdala, entorhinal cortex and prefrontal cortex.”
- Also stated in: § 2. PERINEURONAL NET ABNORMALITIES IN SCHIZOPHRENIA · plain
“Lower numbers of WFA-labeled PNNs were detected in the amygdala, entorhinal and prefrontal cortex (Mauney et al., 2013; Pantazopoulos et al., 2010).”
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What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § 2. PERINEURONAL NET ABNORMALITIES IN SCHIZOPHRENIA · plain
In the paper
“The distribution of these changes matches closely not only the normal distribution of WFA-labeled PNNs, but also that of GABAergic interneurons expressing PVB (Pantazopoulos et al., 2010).”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > 2. PERINEURONAL NET ABNORMALITIES IN SCHIZOPHRENIA
What the sources say
- Not checked yetcites Pantazopoulos et al., 2010 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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
“This result confirms the association of WFA-labeled PNNs with PVB-positive neurons, yet indicates that about a third of these PNNs ensheaths other neuronal populations. Among these are interneurons expressing somatostatin (Fig. 4; unpublished data), a particular interesting neuronal population in light of their expression of the voltage-gated potassium channel subunit Kv3, which may confer them”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > 1. PERINEURONAL NETS: COMPOSITION AND ASSOCIATION WITH DISTINCT NEURONAL POPULATIONS
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“Our results show that only approximately 54% of aggrecan-labeled PNNs were co-labeled with WFA.”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > 1. PERINEURONAL NETS: COMPOSITION AND ASSOCIATION WITH DISTINCT NEURONAL POPULATIONS
What the sources say
- Not checked yetcites Pantazopolous et al., 2014
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“Numbers of PNN immunolabeled for CS-6 (Pantazopolous et al., 2014), WFA, and v0/v1 isoforms of the CSPG versican were normal in this nucleus (Fig. 3; unpublished data).”
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What the sources say
- Not checked yetcites Pantazopolous et al., 2014
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“In contrast, decreases of CS-6 immunoreactive PNNs were detected broadly across several amygdala nuclei, including the lateral, basal, accessory basal, cortical, and medial nuclei.”
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What the sources say
- Not checked yetcites Pantazopolous et al., 2014
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Remarkably, the central nucleus of the amygdala appears to be spared by these abnormalities in SZ.”
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What the sources say
- Not checked yetcites Pantazopolous et al., 2014
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“Our results show marked reductions of aggrecan- and CS6-positive PNNs in the amygdala SZ subjects (effect size, aggrecan g=−0.82; 3B3 g= −1.71) (Fig. 5).”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > 2. PERINEURONAL NET ABNORMALITIES IN SCHIZOPHRENIA
What the sources say
- Not checked yetcites Pantazopolous et al., 2014
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Recent findings from our group show that decreases of PNNs in the amygdala of subjects with SZ are accompanied by marked reductions of glial cells expressing aggrecan and CS6 sulfation (Pantazopoulos, submitted for publication).”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > 4. POTENTIAL CAUSES OF PNN ABNORMALITIES > 4.1 Decreased CSPG Availability May Contribute to PNN Decreases in SZ
What the sources say
- Not checked yetcites Pantazopoulos, submitted for publication
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- It may state two separate claims as one. 39
- Probably not a substantial claim. 7
None of the sources cited for this claim have been checked yet.
In the paper
“Notably, numbers of these neurons were normal in the amygdala and entorhinal cortex, and densities of WFA-labeled PNNs were unchanged in the central nucleus of the amygdala and visual cortex of subjects with SZ (Mauney et al., 2013; Pantazopoulos et al., 2010)(Fig. 3, unpublished data).”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > 2. PERINEURONAL NET ABNORMALITIES IN SCHIZOPHRENIA
What the sources say
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“PNNs labeled with the CS-6 sulfation antibody 3B3 were substantially more numerous, and displayed a broader distribution in the human amygdala with respect to WFA-labeled PNNs.”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > 1. PERINEURONAL NETS: COMPOSITION AND ASSOCIATION WITH DISTINCT NEURONAL POPULATIONS
What the sources say
- Not checked yetcites Pantazopolous et al., 2014
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Within each brain structure examined, WFA-labeled PNN reductions were selective for distinct subregions, i.e. the lateral nucleus of the amygdala, superficial layers of the entorhinal cortex and layers III and V of the prefrontal cortex.”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > 2. PERINEURONAL NET ABNORMALITIES IN SCHIZOPHRENIA
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“In the human amygdala, 68% of WFA-labeled PNNs envelop PVB-positive neurons, a small percentage of which also express calbindin (Pantazopoulos et al., 2006).”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > 1. PERINEURONAL NETS: COMPOSITION AND ASSOCIATION WITH DISTINCT NEURONAL POPULATIONS
What the sources say
- Not checked yetcites Pantazopoulos et al., 2006 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
“Furthermore, PNNs containing versican (v0/v1 isoform) were detected selectively in the central nucleus (Fig. 3), but not in other amygdala nuclei, and represented a clearly distinct population with respect to those containing WFA (unpublished observations).”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > 1. PERINEURONAL NETS: COMPOSITION AND ASSOCIATION WITH DISTINCT NEURONAL POPULATIONS
Strength:boosted· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“In the lateral nucleus, 49% of 3B3-IR PNNs are co-labeled with WFA; this percentage decreases drastically in the other amygdala nuclei where the large majority of PNNs was 3B3-positive but WFA-negative.”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > 1. PERINEURONAL NETS: COMPOSITION AND ASSOCIATION WITH DISTINCT NEURONAL POPULATIONS
What the sources say
- Not checked yetcites Pantazopolous et al., 2014
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Decreases of aggrecan-immunoreactive PNNs were selective for the lateral nucleus of the amygdala, similar to previous observations using WFA.”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > 2. PERINEURONAL NET ABNORMALITIES IN SCHIZOPHRENIA
What the sources say
- Not checked yetcites Pantazopolous et al., 2014
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Consistently, in the human PFC, numbers of PNNs gradually increase from childhood through early adulthood, consistent with their role in regulating human prefrontal cortex circuit refinement (Mauney et al., 2013).”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > 3. FUNCTIONAL IMPLICATIONS OF PNN ABNORMALITIES IN SCHIZOPHRENIA > 3.2 PNN Regulation of Synaptic Plasticity and Learning
What the sources say
- Not checked yetcites Mauney et al., 2013 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“This regulation occurs through families of matrix metalloproteinases that cleave ECM components, altering their functions and affecting plasticity.”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
In the paper
“Immunolabeling using antibodies against CSPG protein cores or sulfation patterns shows that PNNs are heterogeneous in composition, with only a subgroup labeled by WFA.”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > 1. PERINEURONAL NETS: COMPOSITION AND ASSOCIATION WITH DISTINCT NEURONAL POPULATIONS
What the sources say
- Not checked yetcites Ajmo et al., 2008
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Like WFA-labeled PNNs, 3B3-labeled PNNs show clear interneuron-like morphology, suggesting that a large population of interneurons in the amygdala is associated with 3B3-labeled PNNs (see also below).”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > 1. PERINEURONAL NETS: COMPOSITION AND ASSOCIATION WITH DISTINCT NEURONAL POPULATIONS
What the sources say
- Not checked yetcites Pantazopolous et al., 2014
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Perineuronal nets (PNNs), first described by Camillo Golgi in 1898, are specialized aggregates of extracellular matrix (ECM) molecules surrounding the somata, dendrites and proximal axon segment of distinct neuronal populations (Fig. 1) (Brauer et al., 1993; Celio et al., 1998; Golgi, 1898; Kwok et al., 2011; Seeger et al., 1994; Spreafico et al., 1999; Vitellaro-Zuccarello et al., 1998).”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > INTRODUCTION
What the sources say
- Not checked yetcites Brauer et al., 1993
- Not checked yetcites Celio et al., 1998 source
- Not checked yetcites Golgi, 1898
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably 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
“Notably, the composition of PNNs is regulated dynamically in response to factors such as fear, reward, stress, and immune response.”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > Abstract
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. 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
“Several metalloproteinases have been proposed as vulnerability factors for schizophrenia.”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Importantly, other PNN elements, namely Reelin and semaphorin 3A, have been shown to be involved in the pathophysiology of SZ, although not directly as PNN components (Abdolmaleky et al., 2005a; Carulli et al.,”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > INTRODUCTION
What the sources say
- Not checked yetcites Abdolmaleky et al., 2005a
- Not checked yetcites Carulli et al., 2013a
- Not checked yetcites Costa et al., 2001
Strength:boosted· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“As an example, in the amygdala of rhesus monkey, the overwhelming majority of WFA-positive PNNs ensheath neurons expressing glutamic acid decarboxylase (GAD), a typical marker for GABAergic neurons, with many of these neurons also expressing PVB and/or calbindin (Hartig et al., 1995).”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > 1. PERINEURONAL NETS: COMPOSITION AND ASSOCIATION WITH DISTINCT NEURONAL POPULATIONS
What the sources say
- Not checked yetcites Hartig et al., 1995 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
“CSPGs, the organizers of the ECM, are highly represented in PNNs, with aggrecan, neurocan, brevican, versican and phosphacan among the most abundant (Deepa et al., 2006; Giamanco and Matthews, 2012; Yamaguchi, 2000).”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > 1. PERINEURONAL NETS: COMPOSITION AND ASSOCIATION WITH DISTINCT NEURONAL POPULATIONS
What the sources say
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
“Yet, they are restricted in their distribution to specific cortical layers and amygdala nuclei, suggesting specialized mechanisms affecting distinct neuronal populations.”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > 2. PERINEURONAL NET ABNORMALITIES IN SCHIZOPHRENIA
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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In the paper
“Such disruption may contribute to increased amygdala activity, consistent with observation in SZ subjects tonically and during the processing of emotional stimuli (Holt et al., 2006; Rauch et al., 2010; Suslow et al., 2013; Taylor et al., 2005).”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > 3. FUNCTIONAL IMPLICATIONS OF PNN ABNORMALITIES IN SCHIZOPHRENIA > 3.1 PNN Regulation of Synaptic Functions
What the sources say
- Not checked yetcites Holt et al., 2006
- Not checked yetcites Rauch et al., 2010
- Not checked yetcites Suslow et al., 2013
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“Together, these findings suggest that reductions of WFA-labeled PNNs in SZ do not simply reflect loss of PVB-expressing neurons, and impact selective populations of these neurons in a region-selective manner.”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > 2. PERINEURONAL NET ABNORMALITIES IN SCHIZOPHRENIA
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“This process, proposed to represent a fundamental mechanism for the maintenance of synaptic receptor pools, has been shown to controlled by PNNs, which restricted the lateral diffusion of AMPA receptors and thus allow synaptic desensitization (Frischknecht and Gundelfinger, 2012; Frischknecht et al., 2009; Heine et al., 2008).”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > 3. FUNCTIONAL IMPLICATIONS OF PNN ABNORMALITIES IN SCHIZOPHRENIA > 3.1 PNN Regulation of Synaptic Functions
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“The considerations above highlight the effects of PNNs on synaptic functions and support the idea that PNN disruption in SZ may result in synaptic dysregulation and altered firing properties of PNN-bearing neurons.”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > 3. FUNCTIONAL IMPLICATIONS OF PNN ABNORMALITIES IN SCHIZOPHRENIA > 3.1 PNN Regulation of Synaptic Functions
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“In this study, PNN enzymatic degradation in the ventral hippocampus resulted in increased activity of pyramidal neurons, postulated to result from disruption of GABAergic neuronal activity following PNN loss (Shah and Lodge, 2013).”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > 3. FUNCTIONAL IMPLICATIONS OF PNN ABNORMALITIES IN SCHIZOPHRENIA > 3.1 PNN Regulation of Synaptic Functions
What the sources say
- Not checked yetcites Shah and Lodge, 2013 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“These abnormalities are large in magnitude, robust to confounding factors and shared by several brain regions involved in SZ (Mauney et al., 2013; Pantazopolous et al., 2014; Pantazopoulos et al., 2010).”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > 2. PERINEURONAL NET ABNORMALITIES IN SCHIZOPHRENIA
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“However, only one-third (30%) of WFA-positive PNNs also expresses aggrecan, raising the possibility that neuronal populations affected by WFA- and aggrecan-positive PNN loss only partially overlap.”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > 2. PERINEURONAL NET ABNORMALITIES IN SCHIZOPHRENIA
What the sources say
- Not checked yetcites Pantazopolous et al., 2014
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Localized enzymatic CSPG digestion in adult animals caused a reversal to a juvenile form of fear conditioning, one that can be fully erased by extinction (Gogolla et al., 2009; Kim and Richardson, 2007).”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > 3. FUNCTIONAL IMPLICATIONS OF PNN ABNORMALITIES IN SCHIZOPHRENIA > 3.2 PNN Regulation of Synaptic Plasticity and Learning
What the sources say
- Not checked yetcites Gogolla et al., 2009 source
- Not checked yetcites Kim and Richardson, 2007
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In subjects with SZ, decreases of PNNs in multiple brain regions were robust to confounding variables, including exposure to pharmacological agents, and did not correlate with age at onset of the disease or duration of illness (Mauney et al., 2013; Pantazopolous et al., 2014; Pantazopoulos et al., 2010).”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > 4. POTENTIAL CAUSES OF PNN ABNORMALITIES
What the sources say
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“In their experiments, CSPG/PNN degradation in the amygdala in combination with extinction training resulted in erasure of drug (cocaine, morphine)-related memories, facilitated the extinction of drug-seeking behavior and prevented the spontaneous recovery and drug-induced reinstatement of drug-seeking behavior (Xue et al., 2014).”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > 3. FUNCTIONAL IMPLICATIONS OF PNN ABNORMALITIES IN SCHIZOPHRENIA > 3.2 PNN Regulation of Synaptic Plasticity and Learning
What the sources say
- Not checked yetcites Xue et al., 2014 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Glial cells are a main source of chondroitin sulfate proteoglycans (abbreviated here as CSPGs), and have been shown to critically contribute to the formation and maintenance of PNNs (Faissner et al., 2010; John et al., 2006; Klausmeyer et al., 2011; Wiese et al., 2012).”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > 4. POTENTIAL CAUSES OF PNN ABNORMALITIES > 4.1 Decreased CSPG Availability May Contribute to PNN Decreases in SZ
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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 observations are consistent with the idea that PNN abnormalities in SZ may be inherent to this disorder and, perhaps, present at its onset.”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > 4. POTENTIAL CAUSES OF PNN ABNORMALITIES
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“As proposed by Do and coworkers, the protection afforded to GABAergic neurons by PNNs might reflect a balance between the oxidative burden on these ECM structures and the capacity of the system to maintain them (Cabungcal et al., 2013).”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > 3. FUNCTIONAL IMPLICATIONS OF PNN ABNORMALITIES IN SCHIZOPHRENIA > 3.3 Oxidative Stress
What the sources say
- Not checked yetcites Cabungcal et al., 2013 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“The implementation of this adult form of ECM coincides with the closure of critical periods of postnatal development, during which neuronal circuits are shaped by experience, and culminates with the maturation of PNNs and PNN-like perisynaptic ECM aggregates (Balmer et al., 2009; Gogolla et al., 2009; Gundelfinger et al., 2010; McRae et al., 2007; Nowicka et al., 2009; Pizzorusso et al., 2002;”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > 3. FUNCTIONAL IMPLICATIONS OF PNN ABNORMALITIES IN SCHIZOPHRENIA > 3.2 PNN Regulation of Synaptic Plasticity and Learning
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“PNN gradual maturation around somata and dendrites stabilizes successful synapses, restricting plasticity, regulating synaptogenesis and maintaining mature forms of learning (Bukalo et al., 2001; Carulli et al., 2013b; Dityatev et al., 2007; Faissner et al., 2010; Gundelfinger et al., 2010; McRae and Porter, 2012; Pyka et al., 2011).”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > 3. FUNCTIONAL IMPLICATIONS OF PNN ABNORMALITIES IN SCHIZOPHRENIA > 3.2 PNN Regulation of Synaptic Plasticity and Learning
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“Together, this evidence suggests that PNN abnormalities in SZ may profoundly impact emotion processing and plasticity.”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > 3. FUNCTIONAL IMPLICATIONS OF PNN ABNORMALITIES IN SCHIZOPHRENIA > 3.2 PNN Regulation of Synaptic Plasticity and Learning
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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 considerations suggest that reduced availability of CSPGs, perhaps in part due to genetic factors, may lead to a failure to form PNNs during late development, potentially disrupting the maturation of inhibitory neural circuits in SZ.”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > 4. POTENTIAL CAUSES OF PNN ABNORMALITIES > 4.1 Decreased CSPG Availability May Contribute to PNN Decreases in SZ
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The main agents of this remodeling process are three families of metalloproteases collectively known as metzincin family, i.e. ‘matrix metalloproteases’ (MMPs), ‘a disintegrin and matrix metalloproteases’ (ADAMS), and ‘ADAMS with a thrombospondin domain’ (ADAMTS), which cleave ECM molecules, including those that compose PNNs (Fig.2)”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > 4. POTENTIAL CAUSES OF PNN ABNORMALITIES > 4.2 Disruption of ECM remodeling may contribute to PNN decreases in SZ
What the sources say
- Not checked yetcites Abdolmaleky et al., 2005b
- Not checked yetcites Hobohm et al., 2005 source
- Not checked yetcites Medina-Flores et al., 2004
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“These responses have been linked to the pathogenesis of SZ, with a very recent study pointing to a genetic contribution to immune factors involvement (Arion et al., 2007; Fillman et al., 2013; Horvath and Mirnics, 2014; Ripke and Schizophrenia Working Group of the Psychiatric Genomics, 2014; Saetre et al., 2007; Smith et al., 2007).”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > 4. POTENTIAL CAUSES OF PNN ABNORMALITIES > 4.2 Disruption of ECM remodeling may contribute to PNN decreases in SZ
What the sources say
- Not checked yetcites Arion et al., 2007
- Not checked yetcites Fillman et al., 2013
- Not checked yetcites Horvath and Mirnics, 2014
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
“Thus, interactions between disregulated stress response and immune systems in subjects with SZ may impact expression of metalloproteases, resulting in degradation of PNNs.”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > 4. POTENTIAL CAUSES OF PNN ABNORMALITIES > 4.2 Disruption of ECM remodeling may contribute to PNN decreases in SZ
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Mechanisms of PNN regulation and metalloprotease function found in animal and non-schizophrenia studies apply to human schizophrenia.
None of the sources cited for this claim have been checked yet.
In the paper
“For instance, expression of MMP9 was shown to increase in the amygdala, prefrontal cortex, and hippocampus during contextual fear learning, while pharmacological disruption of MMP activity results in disruption of reconsolidation of fear memory (Brown et al., 2009; Ganguly et al., 2013).”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > 4. POTENTIAL CAUSES OF PNN ABNORMALITIES > 4.2 Disruption of ECM remodeling may contribute to PNN decreases in SZ
What the sources say
- Not checked yetcites Brown et al., 2009
- Not checked yetcites Ganguly et al., 2013
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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 metalloproteases expression, during development and/or adulthood, would result in dysregulation of ECM remodeling with consequent failure of PNN maturation and impaired PNN stability.”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > 4. POTENTIAL CAUSES OF PNN ABNORMALITIES > 4.2 Disruption of ECM remodeling may contribute to PNN decreases in SZ
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Mechanisms of PNN regulation and metalloprotease function found in animal and non-schizophrenia studies apply to human schizophrenia.
- Rests on an assumption: Changes in mRNA levels of MMPs and ADAMTSs in schizophrenia indicate corresponding changes in protease activity that can degrade PNNs.
None of the sources cited for this claim have been checked yet.
In the paper
“Notably, metalloproteases play a key role in synaptic plasticity and memory, creating windows of opportunity for learning by temporarily releasing neurons from the ECM clamping effects on plasticity and increasing synaptogenesis (Frischknecht and Gundelfinger, 2012; Rivera et al., 2010; Van Hove et al., 2012; Wright and Harding, 2009).”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > 4. POTENTIAL CAUSES OF PNN ABNORMALITIES > 4.2 Disruption of ECM remodeling may contribute to PNN decreases in SZ
What the sources say
- Not checked yetcites Frischknecht and Gundelfinger, 2012 source
- Not checked yetcites Rivera et al., 2010
- Not checked yetcites Van Hove et al., 2012
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“PNN abnormalities may represent an important factor in the pathophysiology of SZ, contributing to a disruption of GABAergic circuits observed in this disorder.”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > CONCLUSIONS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Mechanisms of PNN regulation and metalloprotease function found in animal and non-schizophrenia studies apply to human schizophrenia.
- Rests on an assumption: Changes in mRNA levels of MMPs and ADAMTSs in schizophrenia indicate corresponding changes in protease activity that can degrade PNNs.
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
“and in turn impact postnatal neuronal maturation, protection from oxidative stress, synaptic regulation and plasticity of distinct interneuronal populations, potentially accounting for molecular and functional anomalies in intrinsic inhibitory circuits.”
§ LOSING THE SUGAR COATING: POTENTIAL IMPACT OF PERINEURONAL NET ABNORMALITIES ON INTERNEURONS IN SCHIZOPHRENIA > CONCLUSIONS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes? Based: unclearIt may state two separate claims as one.
- Rests on an assumption: Mechanisms of PNN regulation and metalloprotease function found in animal and non-schizophrenia studies apply to human schizophrenia.
The paper relies on this without support.
Mechanisms of PNN regulation and metalloprotease function found in animal and non-schizophrenia studies apply to human schizophrenia.
“For instance, expression of MMP9 was shown to increase in the amygdala, prefrontal cortex, and hippocampus during contextual fear learning, while pharmacological disruption of MMP activity results in disruption of reconsolidation of fear memory (Brown et al., 2009; Ganguly et al., 2013).”
The paper relies on this without support.
Changes in mRNA levels of MMPs and ADAMTSs in schizophrenia indicate corresponding changes in protease activity that can degrade PNNs.
“Consistent with this hypothesis, a recent gene expression profiling study of the superior temporal gyrus in subjects with SZ showed altered mRNA expression of MMPs and ADAMTSs, including MMP16 (Pietersen et al., 2014).”
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?
In the citing paper
“As PNNs regulate GABAergic cell function and oxidative stress levels, cortical abnormalities observed in schizophrenia may be attributed to PNN dysfunction (reviewed in Berretta, 2012; Berretta et al., 2015).”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Berretta et al., 2015
In the citing paper
“Most cortical PV neurons, and a small number of PCs, are ensheathed by perineuronal nets (PNNs), a condensed form of extracellular matrix (Berretta et al, 2015)”
From Reduced Labeling of Parvalbumin Neurons and Perineuronal Nets in the Dorsolateral Prefrontal Cortex of Subjects with Schizophrenia (2016) · cites this paper as Berretta et al, 2015
Citations
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Flagged first, then by citations
3 of the 189 references couldn’t be matched to a known paper.
Research works printed but not linked: 3
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Sikder, S., & Bozdagi-Gunal, O. (2026) · Brain Science Advances · doi:10.26599/bsa.2026.905017
Metadata
- Authors
- Berretta, S., Pantazopoulos, H., Markota, M., Brown, C., & Batzianouli, E. T.
- Affiliations
- Harvard University (US)
- McLean Hospital (US)
- Corresponding author
- Berretta, Sabina
- Venue
- Schizophrenia Research
- Publisher
- Elsevier BV
- Published
- 2015-09
- Volume
- 167
- Issue
- 1-3
- Pages
- 18-27
- ISSN
- 0920-9964 (ISSN-L)
- PMC
- PMC4504843
- OpenAlex
- W2067214903
- Semantic Scholar
- c81328ae42747c9add123967a8c1386cf4efc26a
- Cited by
- 152
- References
- 189
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 9 · 2023: 6 · 2022: 15 · 2021: 20 · 2020: 8 · 2019: 12 · 2018: 23 · 2017: 24 · 2016: 14 · 2015: 9
- FWCI
- 3.21
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Schizophrenia Research (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (acceptedVersion)
- Funders
- National Institute of Mental Health (MH091348, MH083222, MH086522, R01MH091348, R01MH086522, R21MH083222)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- perineuronal nets, schizophrenia
- MeSH terms
- Animals, Brain, Extracellular Matrix, gamma-Aminobutyric Acid, Humans, Interneurons, Schizophrenia
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.
What counts as a claim ›How we measure confidence ›How we check this ›
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