Perineuronal nets protect fast-spiking interneurons against oxidative stress

• DOI: 10.1073/pnas.1300454110
• Publication Date: 2013-05-14T04:55:35Z
• Authors: Jan-Harry Cabungcal; Pascal Steullet; Hirofumi Morishita; Rudolf Kraftsik; Michel Cuenod; Takao K. Hensch; Kim Q. Do
• Keywords: Perineuronal net; Proteostasis; Interneuron

A hallmark of schizophrenia pathophysiology is the dysfunction cortical inhibitory GABA neurons expressing parvalbumin, which are essential for coordinating neuronal synchrony during various sensory and cognitive tasks. The high metabolic requirements these fast-spiking cells may render them susceptible to redox dysregulation oxidative stress. Using mice carrying a genetic imbalance, we demonstrate that extracellular perineuronal nets, constitute specialized polyanionic matrix enwrapping most interneurons as they mature, play critical role in protection against These nets limit effect genetically impaired antioxidant systems and/or excessive reactive oxygen species produced by severe environmental insults. We observe an inverse relationship between robustness around parvalbumin degree intracellular stress display. Enzymatic degradation renders mature fast rhythmic more In parallel, enwrapped with better protected than immature surrounded less-condensed nets. Although act protective shield, also themselves sensitive excess might therefore reflect balance burden on net capacity system maintain Abnormal observed postmortem patient brain, thus underlie vulnerability functional impairment pivotal circuits schizophrenia.