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Neuropharmacology. 2012 Mar;62(3):1322-31. doi: 10.1016/j.neuropharm.2011.01.049. Epub 2011 Feb 17.

Behavioral and neurochemical consequences of cortical oxidative stress on parvalbumin-interneuron maturation in rodent models of schizophrenia.

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Department of Psychiatry, University of California, San Diego, MC0804, La Jolla, CA 92093-0804, USA.


Oxidative stress, in response to the activation of the superoxide-producing enzyme Nox2, has been implicated in the schizophrenia-like behavioral dysfunction that develops in animals that were subject to either neonatal NMDA receptor-antagonist treatment or social isolation. In both of these animal models of schizophrenia, an environmental insult occurring during the period of active maturation of the fast-spiking parvalbumin-positive (PV+) interneuronal circuit leads to a diminished expression of parvalbumin in GABA-inhibitory neurons when animals reach adulthood. The loss of PV+ interneurons in animal models had been tentatively attributed to the death of these neurons. However, present results show that for the perinatal NMDA-R antagonist model these interneurons are still alive when animals are 5-6 weeks of age even though they have lost their phenotype and no longer express parvalbumin. Alterations in parvalbumin expression and sensory-evoked gamma-oscillatory activity, regulated by PV+ interneurons, are consistently observed in schizophrenia. We propose that cortical networks consisting of faulty PV+ interneurons interacting with pyramidal neurons may be responsible for the aberrant oscillatory activity observed in schizophrenia. Thus, oxidative stress during the maturation window for PV+ interneurons by alteration of normal brain development, leads to the emergence of schizophrenia-like behavioral dysfunctions when subjects reach early adulthood.

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