Sex differences and estrogen regulation of BDNF gene expression, but not propeptide content, in the developing hippocampus.
Sex differences and estrogen regulation of BDNF gene expression, but not propeptide content, in the developing hippocampus.
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DOI：
10.1002/jnr.23920
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发表时间：
2017-01-02
影响因子：
4.2
通讯作者：
McCarthy, Margaret M.
中科院分区：
文献类型：
--
作者：
Kight, Katherine E.;McCarthy, Margaret M.
成人脑功能的性别差异通常是通过产前和产后早期敏感时期类固醇激素的作用在发育过程中确定的。在啮齿类动物中，发育中的大脑的各种细胞终点受到雌二醇的影响，雌二醇来源于循环睾酮的芳构化和/或在大脑内合成。我们以前曾描述过一种性别差异的神经发生在新生大鼠海马是由雌二醇调制。在这份报告中，我们研究了一个潜在的下游调节器的影响，雌二醇对海马细胞增殖的脑源性神经营养因子（BDNF）的基因表达的男性和女性新生大鼠在响应雌二醇。与女性相比，男性在海马齿状回和CA 1区有更高的Bdnf基因表达。新生儿管理的外源性雌二醇导致相反的影响BDNF的表达在这些地区的新生儿海马，如BDNF的转录增加CA 1，但减少在齿状回。通过拮抗雌激素受体阻断内源性雌二醇信号传导降低了雄性大鼠齿状核中BDNF的表达，但对雌性大鼠没有影响，对CA 1区也没有影响。有趣的是，这种性别差异和对雌二醇的反应并不反映在翻译输出上，因为没有观察到BDNF前体肽的差异。雌二醇对新生儿海马BDNF表达的性别和区域特异性影响表明，这些多效性因子在调节发育神经发生中存在复杂的功能关系。在新生大鼠海马中，雄性大鼠在齿状回和阿蒙角有更多的BDNF基因转录本。雌二醇信号的操纵对出生后早期BDNF基因表达具有区域和性别特异性影响。
Sex differences in adult brain function are frequently determined developmentally through the actions of steroid hormones during sensitive periods of prenatal and early postnatal life. In rodents, various cellular endpoints of the developing brain are affected by estradiol that is derived from the aromatization of circulating testosterone and/or synthesized within the brain. We have previously described a sex difference in neurogenesis in the hippocampus of neonatal rats that is modulated by estradiol. In this report, we examined a potential downstream regulator of the effects of estradiol on hippocampal cell proliferation by measuring gene expression of brain-derived neurotrophin (BDNF) in male and female neonatal rats in response to estradiol. Males had higher baseline Bdnf gene expression in dentate gyrus and CA1 regions of the hippocampus, compared to females. Neonatal administration of exogenous estradiol resulted in opposite effects on Bdnf expression in these areas of the neonatal hippocampus, such that Bdnf transcripts increased in CA1 but decreased in dentate. Blocking endogenous estradiol signaling by antagonizing estrogen receptors decreased Bdnf expression in the dentate of males, but not females, and had no effect in CA1. Interestingly, this sex difference and response to estradiol was not mirrored by translational output, as no differences in BDNF precursor peptide were observed. The sex- and region-specific effects of estradiol on Bdnf expression in the neonatal hippocampus suggest a complex functional relationship between these pleiotropic factors in regulating developmental neurogenesis. In the hippocampus of neonatal rats, males have more Bdnf gene transcripts in the dentate gyrus and Ammon’s horn. Manipulation of estradiol signaling has region- and sex-specific effects on Bdnf gene expression during the early postnatal period.
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