title: Neuroendocrine profile in a rat model of psychosocial stress: relation to oxidative stress.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  Pharmacological targeting of NOX2 might be of crucial importance for the treatment of psychosocial stress-induced psychosis.
authors: Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.
authors: Marilena
authors: M
authors: Colaianna
authors: Stefania
authors: S
authors: Schiavone
authors: Margherita
authors: M
authors: Zotti
authors: Paolo
authors: P
authors: Tucci
authors: Maria Grazia
authors: MG
authors: Morgese
authors: Liselotte
authors: L
authors: Bäckdahl
authors: Rikard
authors: R
authors: Holmdahl
authors: Karl-Heinz
authors: KH
authors: Krause
authors: Vincenzo
authors: V
authors: Cuomo
authors: Luigia
authors: L
authors: Trabace
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000098:Acetophenones / Q000494:pharmacology; D000311:Adrenal Glands / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D015415:Biomarkers / Q000097:blood; D003345:Corticosterone / Q000097:blood*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D009154:Mutation; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D009490:Neurosecretory Systems / Q000378:metabolism; D018384:Oxidative Stress; D010913:Pituitary-Adrenal System / Q000378:metabolism; D011610:Psychosocial Deprivation; D011618:Psychotic Disorders / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical; D012463:Saliva / Q000378:metabolism; D012934:Social Isolation; D013315:Stress, Psychological / Q000097:blood*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D000098:Acetophenones; D000975:Antioxidants; D015415:Biomarkers; C002744:3-nitrotyrosine; D014443:Tyrosine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D000324:Adrenocorticotropic Hormone; C056165:acetovanillone; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D003849:Deoxyguanosine; D003345:Corticosterone