Perineuronal nets protect fast-spiking interneurons against oxidative stress.

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State: Public
Version: author
Serval ID
serval:BIB_5877A3A31F5D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Perineuronal nets protect fast-spiking interneurons against oxidative stress.
Journal
Proceedings of the National Academy of Sciences of the United States of America
Author(s)
Cabungcal J.H., Steullet P., Morishita H., Kraftsik R., Cuenod M., Hensch T.K., Do K.Q.
ISSN
1091-6490 (Electronic)
ISSN-L
0027-8424
Publication state
Published
Issued date
2013
Peer-reviewed
Oui
Volume
110
Number
22
Pages
9130-9135
Language
english
Notes
Publication types: Journal Article Publication Status: ppublish
Abstract
A hallmark of schizophrenia pathophysiology is the dysfunction of cortical inhibitory GABA neurons expressing parvalbumin, which are essential for coordinating neuronal synchrony during various sensory and cognitive tasks. The high metabolic requirements of these fast-spiking cells may render them susceptible to redox dysregulation and oxidative stress. Using mice carrying a genetic redox imbalance, we demonstrate that extracellular perineuronal nets, which constitute a specialized polyanionic matrix enwrapping most of these interneurons as they mature, play a critical role in the protection against oxidative stress. These nets limit the effect of genetically impaired antioxidant systems and/or excessive reactive oxygen species produced by severe environmental insults. We observe an inverse relationship between the robustness of the perineuronal nets around parvalbumin cells and the degree of intracellular oxidative stress they display. Enzymatic degradation of the perineuronal nets renders mature parvalbumin cells and fast rhythmic neuronal synchrony more susceptible to oxidative stress. In parallel, parvalbumin cells enwrapped with mature perineuronal nets are better protected than immature parvalbumin cells surrounded by less-condensed perineuronal nets. Although the perineuronal nets act as a protective shield, they are also themselves sensitive to excess oxidative stress. The protection might therefore reflect a balance between the oxidative burden on perineuronal net degradation and the capacity of the system to maintain the nets. Abnormal perineuronal nets, as observed in the postmortem patient brain, may thus underlie the vulnerability and functional impairment of pivotal inhibitory circuits in schizophrenia.
Pubmed
Web of science
Open Access
Yes
Create date
31/05/2013 11:13
Last modification date
20/08/2019 15:12
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