Perineuronal nets and schizophrenia: The importance of neuronal coatings

Bitanihirwe, Byron K.Y.; Woo, Tsung-Ung W.

doi:10.1016/j.neubiorev.2014.03.018

Cited by 80 publications

(55 citation statements)

References 278 publications

(364 reference statements)

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“…Several PNN proteoglycans, the lecticans, are highly glycosylated, and one, aggrecan, is highly enriched in mature PNNs (Bitanihirwe and Woo, 2014). The density of PNNs labeled with Wisteria floribunda agglutinin (WFA), a lectin that binds to specific carbohydrate moieties on proteoglycans, has been reported to be markedly lower in the entorhinal and prefrontal cortices in schizophrenia (Mauney et al, 2013;Pantazopoulos et al, 2010Pantazopoulos et al, , 2015.…”

Section: Introductionmentioning

confidence: 99%

Reduced Labeling of Parvalbumin Neurons and Perineuronal Nets in the Dorsolateral Prefrontal Cortex of Subjects with Schizophrenia

Enwright

Sanapala

Foglio

et al. 2016

Neuropsychopharmacol

193

139

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Alterations in cortical parvalbumin (PV)-containing neurons, including a reduced density of detectable neurons and lower PV levels, have frequently been reported in the dorsolateral prefrontal cortex (DLPFC) of schizophrenia subjects. Most PV neurons are surrounded by perineuronal nets (PNNs) and the density of PNNs, as detected by Wisteria floribunda agglutinin (WFA) labeling, has been reported to be lower in schizophrenia. However, the nature of these PNN alterations, and their relationship to disease-related changes in PV neurons, has not been assessed. Using confocal microscopy, we quantified the densities and fluorescence intensities of PV neurons and PNNs labeled with WFA or immunoreactive for the major PNN protein, aggrecan, in the DLPFC from schizophrenia and matched comparison subjects. In schizophrenia, the densities of PV cells and of PNNs were not altered; however, the fluorescence intensities of PV immunoreactivity in cell bodies and of WFA labeling and aggrecan immunoreactivity in individual PNNs around PV cells were lower. These findings indicate that the normal complements of PV cells and PNNs are preserved in schizophrenia, but the levels of PV protein and of individual PNN components, especially the carbohydrate moieties on proteoglycans to which WFA binds, are lower. Given the roles of PV neurons in regulating DLPFC microcircuits and of PNNs in regulating PV cellular physiology, the identified alterations in PV neurons and their PNNs could contribute to DLPFC dysfunction in schizophrenia.

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Section: Introductionmentioning

confidence: 99%

Reduced Labeling of Parvalbumin Neurons and Perineuronal Nets in the Dorsolateral Prefrontal Cortex of Subjects with Schizophrenia

Enwright

Sanapala

Foglio

et al. 2016

Neuropsychopharmacol

193

139

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“…2013). These data indicate a potential role of PNNs in the development of schizophrenia and suggest that interventions aimed at increasing levels of PNN components in patients might potentially reduce symptomatology of this disorder (see Berretta, 2012;Bitanihirwe and Woo, 2014;Woo, 2013 for a more extensive review of the role of PNNs in schizophrenia symptomatology).…”

Section: Figurementioning

confidence: 91%

“…Abnormal development of PNNs in schizophrenia might underlie impaired synaptic pruning and prolonged neural plasticity due to lack of synaptic stabilization (Woo, 2013). Furthermore, a reduced ion buffer capacity of the ECM due to reduced expression of PNNs might interfere with normal neurotransmission of fast-spiking inhibitory neurons (Bitanihirwe and Woo, 2014). Thus, reduced PNN levels may contribute to dysfunction of GABAergic interneurons that regulate pyramidal cell activity, which together form functional cortical networks (Mauney et al,…”

Section: Pnns and Schizophreniamentioning

confidence: 99%

Neural ECM in addiction, schizophrenia, and mood disorder

Lubbers

Smit

Spijker

et al. 2014

Progress in Brain Research

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“…In this section, we describe postmortem and preclinical studies that may shed light on the role that PNNs may play in schizophrenia (23, 24, 26). …”

Section: On the Potential Importance Of The Pnn In Schizophreniamentioning

confidence: 99%

“…The onset of schizophrenia occurs during late adolescence or early adulthood, when brain circuitry involving the prefrontal cortex and hippocampus, in addition to other limbic regions, undergoes maturation (2-4). The pathophysiologic features of schizophrenia stem from a variety of aberrant neurobiological underpinnings that ultimately impinge on synaptic plasticity and synaptic connectivity (12-14), including anomalies in cortical myelogenesis (13) and synaptic pruning (12, 15), altered glutamatergic signalling (16-18) and reduced neuropil (19) in conjunction with atypical development of cortical inhibitory circuits (14, 20, 21), dopaminergic pathways (22) and perineuronal nets (PNNs) (23-31). …”

mentioning

confidence: 99%

Weaving a Net of Neurobiological Mechanisms in Schizophrenia and Unraveling the Underlying Pathophysiology

Bitanihirwe

Mauney

Woo

2016

Biological Psychiatry

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Perineuronal nets (PNNs) are enigmatic structures composed of extracellular matrix molecules that encapsulate the soma, dendrites, and axon segments of neurons in a lattice-like fashion. Although the majority of PNNs condense around parvalbumin-expressing GABA(γ-aminobutyric acid)ergic interneurons, some glutamatergic pyramidal cells in the brain are also surrounded by PNNs. Experimental findings suggest pivotal roles of PNNs in the regulation of synaptic formation and function. There has also been an increasing body of evidence linking PNN abnormalities to schizophrenia. Interestingly, the number of PNNs progressively increases during postnatal development until plateauing around the period of late adolescence and early adulthood, which temporally coincides with the age of onset of schizophrenia. Given the established role of PNNs in modulating developmental plasticity, the PNN represents a possible candidate for altering the onset and progression of schizophrenia. Similarly, the reported function of PNNs in regulating the trafficking of glutamate receptors places them in a critical position to modulate synaptic pathology, considered a cardinal feature of schizophrenia. Here we discuss the physiological role of PNNs in neural function, synaptic assembly and plasticity in addition to how they interface with circuit/system mechanisms of cognition. An integrated understanding of these neurobiological processes should provide a better basis to elucidate how PNN abnormalities influence brain function and contribute to the pathogenesis of neurodevelopmental disorders such as schizophrenia.

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Perineuronal nets and schizophrenia: The importance of neuronal coatings

Cited by 80 publications

References 278 publications

Reduced Labeling of Parvalbumin Neurons and Perineuronal Nets in the Dorsolateral Prefrontal Cortex of Subjects with Schizophrenia

Reduced Labeling of Parvalbumin Neurons and Perineuronal Nets in the Dorsolateral Prefrontal Cortex of Subjects with Schizophrenia

Neural ECM in addiction, schizophrenia, and mood disorder

Weaving a Net of Neurobiological Mechanisms in Schizophrenia and Unraveling the Underlying Pathophysiology

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