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

NEUROPHARMACOLOGY

卷:62

Article

Powell, Susan B.²  Sejnowski, Terrence J.^1,3  Behrens, M. Margarita¹ 

[1] Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USA

[2] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA

[3] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA

关键词: Redox;    Parvalbumin;    Fast-spiking;    Gamma oscillations;    GABAergic;    Interleukin-6;    NADPH oxidase;    Schizophrenia;   

DOI  :  10.1016/j.neuropharm.2011.01.049

来源: Elsevier

【 摘 要 】

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+ intemeurons 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. This article is part of a Special Issue entitled 'Schizophrenia'. (C) 2011 Elsevier Ltd. All rights reserved.

【 授权许可】

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