Abstract

Oxidative stress is thought to be involved in the development of behavioral and histopathological alterations in animal models of psychosis. Here we investigate the causal contribution of reactive oxygen species generation by the phagocyte NADPH oxidase NOX2 to neuropathological alterations in a rat model of chronic psychosocial stress. In rats exposed to social isolation, the earliest neuropathological alterations were signs of oxidative stress and appearance of NOX2. Alterations in behavior, increase in glutamate levels and loss of parvalbumin were detectable after 4 weeks of social isolation. The expression of the NOX2 subunit p47 phox was markedly increased in pyramidal neurons of isolated rats, but below detection threshold in GABAergic neurons, astrocytes and microglia. Rats with a loss of function mutation in the NOX2 subunit p47 phox were protected from behavioral and neuropathological alterations induced by social isolation. To test reversibility, we applied the antioxidant/NOX inhibitor apocynin after initiation of social isolation for a time period of 3 weeks. Apocynin reversed behavioral alterations fully when applied after 4 weeks of social isolation, but only partially after 7 weeks. Our results demonstrate that social isolation induces rapid elevations of the NOX2 complex in the brain. Expression of the enzyme complex was strongest in pyramidal neurons and a loss of function mutation prevented neuropathology induced by social isolation. Finally, at least at early stages, pharmacological targeting of NOX2 activity might reverse behavioral alterations. © 2012 Macmillan Publishers Limited All rights reserved.

Autore Pugliese

• Trabace Luigia

Tutti gli autori

• Schiavone S , Jaquet V , Sorce S , Dubois-Dauphin M , Hultqvist M , Bäckdahl L , Holmdahl R , Colaianna M , Cuomo V , Trabace L , Krause Kh

Titolo volume/Rivista

TRANSLATIONAL PSYCHIATRY

Anno di pubblicazione

2012

ISSN

2158-3188

ISBN

Non Disponibile

Numero di citazioni Wos

36

Ultimo Aggiornamento Citazioni

Non Disponibile

Numero di citazioni Scopus

36

Ultimo Aggiornamento Citazioni

Non Disponibile

Settori ERC

Non Disponibile

Codici ASJC

Non Disponibile