|Neuroendocrine profile in a rat model of psychosocial stress: relation to oxidative stress.|
|PMID: 23320850 Owner: NLM Status: MEDLINE|
|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.
|Marilena Colaianna; Stefania Schiavone; Margherita Zotti; Paolo Tucci; Maria Grazia Morgese; Liselotte Bäckdahl; Rikard Holmdahl; Karl-Heinz Krause; Vincenzo Cuomo; Luigia Trabace|
|Type: Journal Article; Research Support, Non-U.S. Gov't|
|Title: Antioxidants & redox signaling Volume: 18 ISSN: 1557-7716 ISO Abbreviation: Antioxid. Redox Signal. Publication Date: 2013 Apr|
|Created Date: 2013-03-15 Completed Date: 2013-08-26 Revised Date: 2014-04-22|
Medline Journal Info:
|Nlm Unique ID: 100888899 Medline TA: Antioxid Redox Signal Country: United States|
|Languages: eng Pagination: 1385-99 Citation Subset: IM|
|APA/MLA Format Download EndNote Download BibTex|
Adrenal Glands / metabolism
Adrenocorticotropic Hormone / blood*
Antioxidants / pharmacology
Biological Markers / blood
Corticosterone / blood*
Deoxyguanosine / analogs & derivatives, metabolism
Hypothalamo-Hypophyseal System / metabolism
Hypothalamus / metabolism
NADPH Oxidase / genetics, metabolism
Neurosecretory Systems / metabolism
Pituitary-Adrenal System / metabolism
Psychotic Disorders / metabolism
Saliva / metabolism
Stress, Psychological / blood*
Tyrosine / analogs & derivatives, metabolism
|0/Acetophenones; 0/Antioxidants; 0/Biological Markers; 3604-79-3/3-nitrotyrosine; 42HK56048U/Tyrosine; 88847-89-6/8-oxo-7-hydrodeoxyguanosine; 9002-60-2/Adrenocorticotropic Hormone; B6J7B9UDTR/acetovanillone; EC 18.104.22.168/NADPH Oxidase; EC 22.214.171.124/neutrophil cytosolic factor 1; G9481N71RO/Deoxyguanosine; W980KJ009P/Corticosterone|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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