Sex differences in CRF1, CRF, and CRFBP expression in C57BL/6J mouse brain across the lifespan and in response to acute stress.

Sex differences in CRF1, CRF, and CRFBP expression in C57BL/6J mouse brain across the lifespan and in response to acute stress.
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DOI:
10.1111/jnc.15157
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发表时间:
2021-08
影响因子:
4.7
通讯作者:
Dong, Hongxin
Dong, Hongxin
中科院分区:
医学2区
文献类型:
--
作者:
Locci, Andrea;Yan, Yan;Rodriguez, Guadalupe;Dong, Hongxin

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促肾上腺皮质激素释放因子及其受体1(CRF 1)介导的信号通路在应激反应中起着重要作用。CRF系统的功能障碍与神经精神疾病有关。然而,CRF系统在大脑发育和衰老过程中的动态变化还没有得到很好的研究。在这项研究中,我们的特点CRF 1,CRF,促肾上腺皮质激素释放因子结合蛋白(CRFBP)的表达在不同的大脑区域的男性和女性C57 BL/6 J小鼠从1至18个月的年龄在基础条件下,以及在急性2小时的束缚应激。我们发现,CRF和CRF 1水平往往增加在海马和下丘脑,并减少在前额叶皮层随着年龄的增长,特别是在18个月的年龄,而CRFBP表达遵循相反的方向在这些大脑区域。我们还观察到这三种蛋白质表达的区域特异性性别差异。例如,CRF的表达在女性比男性在所有的大脑区域检查,除了前额叶皮层。急性应激后,CRF和CRF 1在1、6和12月龄时表达上调,在18月龄时表达下调。与同龄男性相比,女性的变化更大。急性应激后,大部分脑区CRFBP表达减少或保持不变。我们的研究结果表明,大脑CRF 1,CRF和CRFBP的表达在整个生命周期和应激条件下以性别和区域特异性的方式动态变化。CRF系统对应激反应的性别差异可能是应激相关神经精神障碍的病因学原因。
Signaling pathways mediated by corticotropin-releasing factor and its receptor 1 (CRF1) play a central role in stress responses. Dysfunction of the CRF system has been associated with neuropsychiatric disorders. However, dynamic changes in the CRF system during brain development and aging are not well investigated. In this study, we characterized CRF1, CRF, and corticotropin-releasing factor binding protein (CRFBP) expression in different brain regions in both male and female C57BL/6J mice from 1 to 18 months of age under basal conditions as well as after an acute 2-hr-restraint stress. We found that CRF and CRF1 levels tended to increase in the hippocampus and hypothalamus, and to decrease in the prefrontal cortex with aging, especially at 18 months of age, whereas CRFBP expression followed an opposite direction in these brain areas. We also observed area-specific sex differences in the expression of these three proteins. For example, CRF expression was lower in females than in males in all the brain regions examined except the prefrontal cortex. After acute stress, CRF and CRF1 were up-regulated at 1, 6, and 12 months of age, and down-regulated at 18 months of age. Females showed more robust changes compared to males of the same age. CRFBP expression either decreased or remained unchanged in most of the brain areas following acute stress. Our findings suggest that brain CRF1, CRF, and CRFBP expression changes dynamically across the lifespan and under stress condition in a sex- and regional-specific manner. Sex differences in the CRF system in response to stress may contribute to the etiology of stress-related neuropsychiatric disorders.
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