Hippocampal nitric oxide contributes to sex difference in affective behaviors
Hippocampal nitric oxide contributes to sex difference in affective behaviors
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海马一氧化氮导致情感行为的性别差异
DOI：
10.1073/pnas.1207461109
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发表时间：
2012-08-28
影响因子：
11.1
通讯作者：
Zhu, Dong-Ya
中科院分区：
文献类型：
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作者：
Hu, Yao;Wu, Dan-Lian;Zhu, Dong-Ya
女性在情感障碍中占优势的机制尚不清楚。在这里，我们证明海马一氧化氮（NO）在啮齿类动物抑郁样行为的性别差异中发挥着作用。雌性小鼠海马体中一氧化氮的产生量显着降低，并且比同窝雄性小鼠更容易表现出负面情感行为。消除雄性和雌性小鼠之间基础海马一氧化氮水平的差异可以弥补情感行为的性别差距。雌二醇通过雌激素受体-β介导的神经元 NO 合酶表达对海马 NO 产生产生正向控制。因此，女性海马中的低雌激素导致局部 NO 低于男性海马。虽然雌激素在调节情感行为方面具有重要意义，但直接介导情感行为性别差异的不是雌激素，而是海马中的NO，因为海马NO是雌二醇行为效应所必需的，而NO是调节行为的独立因素。由于糖皮质激素的释放，压力促进了男性海马NO的产生，从而导致局部NO过量。相反，由于雌激素减少，压力抑制了女性一氧化氮的产生，从而导致海马一氧化氮短缺。激活 cAMP 反应元件结合蛋白 (CREB) 可以挽救海马内 NO 供体二亚乙基三胺/一氧化氮加合物 (DETA/NONOate) 的抗抑郁样作用，而失活 CREB 则消除海马内 NO 供体 DETA/NONOate 的抗抑郁样作用。我们的研究结果表明了情感行为性别差异背后的分子机制。
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.