A developmental sex difference in hippocampal neurogenesis is mediated by endogenous oestradiol.
A developmental sex difference in hippocampal neurogenesis is mediated by endogenous oestradiol.
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DOI：
10.1186/2042-6410-1-8
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发表时间：
2010-11-22
影响因子：
7.9
通讯作者：
McCarthy MM
中科院分区：
文献类型：
--
作者：
Bowers JM;Waddell J;McCarthy MM
雌二醇是一种类固醇激素，对大脑发育有广泛的影响，是海马结构和功能的有力调节剂。海马体是调节复杂认知和情绪反应的关键大脑区域，与几种精神健康障碍的病因有关，其中许多表现出一定程度的性别差异。成年大鼠脑中的许多性别差异是由雌二醇在敏感发育时期的作用决定的。我们以前曾报道过实验大鼠海马发育中细胞发生率的性别差异。男性平均比女性产生更多的新细胞。目前的研究探讨了外源性和内源性雌二醇对这种性别差异的影响。给新生的雄性和雌性大鼠幼仔注射有丝分裂标记物5-溴-2-脱氧尿苷（BrdU）和雌二醇或抗雌二醇作用的药物。在不同时间点观察对细胞数量、增殖、分化和存活的影响。两组间的显著差异通过双因素或三因素方差分析确定。新生雄鼠的细胞增殖率高于雌鼠。雌二醇处理增加了新生雌性小鼠的细胞增殖，但没有增加雄性小鼠的细胞增殖，并且在CA1区，许多这些细胞分化为神经元。新生儿雌二醇诱导的增殖率增加持续到至少3周龄，提示组织效应。施用芳香化酶抑制剂福美斯坦或雌激素受体拮抗剂他莫昔芬可显著减少雄性小鼠的新细胞数量，但雌性小鼠没有。与雌性相比，内源性雌二醇增加了新生雄性小鼠的细胞增殖率。新生儿神经发生的这种性别差异可能会影响成人在学习策略、应激反应或对损伤或疾病的脆弱性方面的差异。
Oestradiol is a steroid hormone that exerts extensive influence on brain development and is a powerful modulator of hippocampal structure and function. The hippocampus is a critical brain region regulating complex cognitive and emotional responses and is implicated in the aetiology of several mental health disorders, many of which exhibit some degree of sex difference. Many sex differences in the adult rat brain are determined by oestradiol action during a sensitive period of development. We had previously reported a sex difference in rates of cell genesis in the developing hippocampus of the laboratory rat. Males generate more new cells on average than females. The current study explored the effects of both exogenous and endogenous oestradiol on this sex difference. New born male and female rat pups were injected with the mitotic marker 5-bromo-2-deoxyuridine (BrdU) and oestradiol or agents that antagonize oestradiol action. The effects on cell number, proliferation, differentiation and survival were assessed at several time points. Significant differences between groups were determined by two- or thee-Way ANOVA. Newborn males had higher rates of cell proliferation than females. Oestradiol treatment increased cell proliferation in neonatal females, but not males, and in the CA1 region many of these cells differentiated into neurons. The increased rate of proliferation induced by neonatal oestradiol persisted until at least 3 weeks of age, suggesting an organizational effect. Administering the aromatase inhibitor, formestane, or the oestrogen receptor antagonist, tamoxifen, significantly decreased the number of new cells in males but not females. Endogenous oestradiol increased the rate of cell proliferation observed in newborn males compared to females. This sex difference in neonatal neurogenesis may have implications for adult differences in learning strategy, stress responsivity or vulnerability to damage or disease.