کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6228601 1276548 2009 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Involvement of NOX2 in the Development of Behavioral and Pathologic Alterations in Isolated Rats
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی روانپزشکی بیولوژیکی
پیش نمایش صفحه اول مقاله
Involvement of NOX2 in the Development of Behavioral and Pathologic Alterations in Isolated Rats
چکیده انگلیسی

BackgroundSocial stress leads to oxidative stress in the central nervous system, contributing to the development of mental disorders. Loss of parvalbumin in interneurons is an important feature of these diseases. We studied the role of the superoxide-producing nicotinamide adenosine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) in rats exposed to social isolation.MethodsMale rats were kept for 7 weeks in group or in social isolation (n = 6-10 per group). Behavioral tests, immunohistochemistry, and analysis of NOX2 expression were performed at the end of social isolation. Apocynin was given in the drinking water (5 mg/kg/day).ResultsNOX2 was below detection level in the brains of control animals, whereas it was highly expressed in isolated rats, particularly in nucleus accumbens and prefrontal cortex. Indirect markers of oxidative stress (oxidized nucleic acid 8-hydroxy-2′-deoxyguanosine, redox-sensitive transcription factor c-fos, and hypoxia-inducible factor-1α) were increased after social isolation in brain areas with high NOX2 expression. An increase in immunoreactive microglia suggested that oxidative stress could be in part due to NOX2 activation in microglia. In response to social isolation, rats showed increased locomotor activity, decreased discrimination, signs of oxidative stress in neurons, and loss of parvalbumin-immunoreactivity. Treatment of isolated rats with the antioxidant/NOX inhibitor apocynin prevented the behavioral and histopathological alterations induced by social isolation.ConclusionsOur data suggest that NOX2-derived oxidative stress is involved in loss of parvalbumin immunoreactivity and development of behavioral alterations after social isolation. These results provide a molecular mechanism for the coupling between social stress and brain oxidative stress, as well as potential new therapeutic avenues.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biological Psychiatry - Volume 66, Issue 4, 15 August 2009, Pages 384-392
نویسندگان
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