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Antioxid Redox Signal. 2013 Apr 20;18(12):1385-99. doi: 10.1089/ars.2012.4569.

Neuroendocrine profile in a rat model of psychosocial stress: relation to oxidative stress.

Author information

1
Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.

Abstract

AIMS:

Psychosocial stress alters the hypothalamic-pituitary-adrenal axis (HPA-axis). Increasing evidence shows a link between these alterations and oxidant elevation. Oxidative stress is implicated in the stress response and in the pathogenesis of neurologic and psychiatric diseases. NADPH oxidases (NOXs) are a major source of reactive oxygen species (ROS) in the central nervous system. Here, we investigated the contributory role of NOX2-derived ROS to the development of neuroendocrine alterations in a rat model of chronic psychosocial stress, the social isolation.

RESULTS:

Significant elevations in the hypothalamic levels of corticotropin-releasing factor and plasmatic adrenocorticotropic hormone were observed from 4 weeks of social isolation. Increased levels of peripheral markers of the HPA-axis (plasmatic and salivary corticosterone) were observed at a later time point of social isolation (7 weeks). Alteration in the exploratory activity of isolated rats followed the same time course. Increased expression of markers of oxidative stress (8-hydroxy-2-deoxyguanosine [8OhdG] and nitrotyrosine) and NOX2 mRNA was early detectable in the hypothalamus of isolated rats (after 2 weeks), but later (after 7 weeks) in the adrenal gland. A 3-week treatment with the antioxidant/NOX inhibitor apocynin stopped the progression of isolation-induced alterations of the HPA-axis. Rats with a loss-of-function mutation in the NOX2 subunit p47(phox) were totally protected from the alterations of the neuroendocrine profile, behavior, and increased NOX2 mRNA expression induced by social isolation.

INNOVATION:

We demonstrate that psychosocial stress induces early elevation of NOX2-derived oxidative stress in the hypothalamus and consequent alterations of the HPA-axis, leading ultimately to an altered behavior.

CONCLUSION:

Pharmacological targeting of NOX2 might be of crucial importance for the treatment of psychosocial stress-induced psychosis.

PMID:
23320850
PMCID:
PMC3603501
DOI:
10.1089/ars.2012.4569
[Indexed for MEDLINE]
Free PMC Article

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