Hippocampal nitric oxide contributes to sex difference in affective behaviors

Hu Y.; Wu D.-L.; Luo C.-X.Zhu L.-J.Zhang J.Wu H.-Y.Zhu D.-Y.

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Hippocampal nitric oxide contributes to sex difference in affective behaviors

机译：Hippocampal nitric oxide contributes to sex difference in affective behaviors

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Mechanisms underlying the female preponderance in affective disorders are poorly understood. Here we show that hippocampal nitric oxide (NO) plays a role in the sex difference of depression-like behaviors in rodents. Female mice had substantially lower NO production in the hippocampus and were significantly more likely to display negative affective behaviors than their male littermates. Eliminating the difference in the basal hippocampal NO level between male and female mice mended the sex gap of affective behaviors. Estradiol exerted a positive control on hippocampal NO production via estrogen receptor-β- mediated neuronal NO synthase expression. Thus, low estrogen in the female hippocampus accounts for lower local NO than in the male hippocampus. Although estrogen has important significance in modulating affective behaviors, it is not estrogen but NO in the hippocampus that mediates the sex difference of affective behaviors directly, because hippocampal NO was necessary for the behavioral effects of estradiol, and NO was an independent factor in modulating behaviors. Stress promoted hippocampal NO production in males because of glucocorticoid release, thus leading to local NO excess. In contrast, stress suppressed NO production in females because of decreased estrogen, thereby resulting in hippocampal NO shortage. Whereas activating cAMP response element binding protein (CREB) rescued the depression-like effects of the intrahippocampal NO donor diethylenetriamine/nitric oxide adduct (DETA/NONOate), inactivating CREB abolished the antidepressant-like effects of the intrahippocampal NO donor DETA/NONOate. Our findings suggest a molecular mechanism underlying the sex difference of affective behaviors.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2012年第35期|14224-14229|共6页
作者
Hu Y.; Wu D.-L.; Luo C.-X.Zhu L.-J.Zhang J.Wu H.-Y.Zhu D.-Y.;
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作者单位

State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China;

Laboratory of Cerebrovascular Disease, Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing 210029, China;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
Chronic mild stress; Corticosterone; Depressive behaviors; Gender difference; Psychiatric disorders;

Hippocampal nitric oxide contributes to sex difference in affective behaviors

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