title: Behavioral and neurochemical consequences of cortical oxidative stress on parvalbumin-interneuron maturation in rodent models of schizophrenia.
abstract: 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.
authors.affiliation: Department of Psychiatry, University of California, San Diego, MC0804, La Jolla, CA 92093-0804, USA.
authors.forename: Susan B
authors.initials: SB
authors.lastname: Powell
authors.forename: Terrence J
authors.initials: TJ
authors.lastname: Sejnowski
authors.forename: M Margarita
authors.initials: MM
authors.lastname: Behrens
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D007395:Interneurons / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009043:Motor Activity / Q000502:physiology; D018384:Oxidative Stress; D010320:Parvalbumins / Q000378:metabolism*; D051381:Rats; D012377:Rodentia; D012559:Schizophrenia / Q000378:metabolism* / Q000473:pathology
chemical_list: D010320:Parvalbumins