Document Detail

Neuroendocrine profile in a rat model of psychosocial stress: relation to oxidative stress.
MedLine Citation:
PMID:  23320850     Owner:  NLM     Status:  Publisher    
Aims: Psychosocial stress alters the 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. NOX enzymes are a major source of ROS in the CNS. 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 CRF and plasmatic ACTH were observed from four weeks of social isolation. Increased levels of peripheral markers of the HPA-axis (plasmatic and salivary corticosterone) were observed at later time point of social isolation (seven weeks). Alteration in exploratory activity of isolated rats followed the same time course. Increased expression of markers of oxidative stress (8OhdG and nitrotyrosine) and NOX2 mRNA was early detectable in the hypothalamus of isolated rats (after two weeks), but later (after seven weeks) in the adrenal gland. A three-weeks-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 p47phox were totally protected from 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 altered behavior. Conclusion: Pharmacological targeting of NOX2 might be of crucial importance for treatment of psychosocial stress-induced psychosis.
Marilena Colaianna; Stefania Schiavone; Margherita Zotti; Paolo Tucci; Maria Grazia Morgese; Liselotte Bäckdahl; Rikard Holmdahl; Karl-Heinz Krause; Vincenzo Cuomo; Luigia Trabace
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-16
Journal Detail:
Title:  Antioxidants & redox signaling     Volume:  -     ISSN:  1557-7716     ISO Abbreviation:  Antioxid. Redox Signal.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100888899     Medline TA:  Antioxid Redox Signal     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
University of Foggia, Department of Clinical and Experimental Medicine, Foggia, Italy, , University of Geneva; Geneva University Hospitals, Department of Pathology and Immunology; Department of Genetic and Laboratory Medicine, Geneva, Switzerland;
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