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Cabungcal JH, Steullet P, Morishita H, Kraftsik R, Cuenod M, Hensch TK, Do KQ. Perineuronal nets protect fast-spiking interneurons against oxidative stress. Proc Natl Acad Sci U S A . 2013 May 28 ; 110(22):9130-5. PubMed Abstract

Comments on Paper and Primary News
Comment by:  John Enwright
Submitted 30 May 2013 Posted 30 May 2013

Multiple studies have demonstrated various roles of perineuronal nets (PNNs) in normal neuronal functions such as regulating synaptic plasticity, ion homeostasis, and critical period closure (Karetko and Skangiel-Kramska, 2009). Furthermore, in subjects with schizophrenia, PNNs have been shown to be disrupted (Pantazopoulos et al., 2010), and other studies have reported evidence of elevated oxidative stress in schizophrenia (Gawryluk et al., 2011). The findings in this paper suggesting a link between the two is intriguing.

A specific population of neurons—cortical fast-spiking, parvalbumin (PV)-positive inhibitory neurons—may be especially vulnerable to oxidative stress. These same neurons are thought to be critical in the generation of γ oscillations, which are thought to underlie working memory, and are disrupted in schizophrenia (Lewis and Sweet, 2009). Interestingly, the authors...  Read more

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Comment by:  Sabina BerrettaHarry Pantazopoulos
Submitted 30 May 2013 Posted 3 June 2013
  I recommend this paper

This elegant study explores the relationships among three potential key factors in the pathophysiology of schizophrenia, i.e., abnormalities affecting neurons expressing parvalbumin, perineuronal nets, and oxidative stress/glutathione reduction.

Perineuronal nets are new players in the field of schizophrenia; in fact, their role in normal brain functions has only recently come to the forefront of neuroscience. These specialized extracellular matrix structures form around the somata, dendrites, and proximal segment of the axon of distinct neuronal populations during late postnatal development (Brückner et al., 2006; Galtrey and Fawcett, 2007). Their activity-driven maturation stabilizes successful synaptic connections and, at least in some brain regions, culminates with the closure of critical periods of development and instatement of adult plastic modalities (Pizzorusso et al., 2002; Gogolla...  Read more

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View all comments by Harry Pantazopoulos

Comment by:  L. Elliot Hong
Submitted 4 June 2013 Posted 4 June 2013

Neural cells in the central nervous system are supported by extracellular structures organized by chondroitin sulphate proteoglycans, also called perineuronal nets (PNNs). This paper by Cabungcal et al., centered on the PNNs, offers a novel mechanism that could potentially integrate several currently somewhat segregated pathophysiologies, i.e., oxidative stress, neural plasticity, excessive dopamine, parvalbumin (PV)-positive GABAergic interneurons, and neural oscillations, all of which have been associated with schizophrenia.

The study showed that degradation of mature PNNs in mice renders PV-immunoreactive cells in the anterior cingulate cortex more vulnerable to chronic oxidative stress. Decrease in PV cells, in turn, leads to reduced local neural oscillations in the β and γ frequency range. The authors also demonstrated that PNNs and PV-interneurons are both sensitive to excessive oxidative stress; immature PV cells in early development may have less PNN protection, and these cells are particularly vulnerable to oxidative stress; and finally, older, but not...  Read more

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