Sex differences in microglial phagocytosis in the neonatal hippocampus.
Sex differences in microglial phagocytosis in the neonatal hippocampus.
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DOI：
10.1016/j.bbi.2017.03.010
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发表时间：
2017-08
期刊：
影响因子：
--
通讯作者：
Lenz KM
中科院分区：
文献类型：
--
作者：
Nelson LH;Warden S;Lenz KM
小胶质细胞通过促进神经发生、支持细胞存活、吞噬祖细胞、新生细胞和死亡细胞等多种途径调控大脑发育。许多相同的发育过程显示出明显的性别差异，但很少有研究评估发育过程中小胶质细胞功能的性别差异。激素诱导的大脑性别分化发生在围产期，因此我们研究了出生后早期海马小胶质细胞形态、吞噬和增殖的性别差异。我们发现新生儿雌性海马明显比雄性海马有更多的吞噬杯状小胶质细胞。我们随后发现，与雄性相比，雌性小胶质细胞吞噬更多的神经祖细胞和健康细胞，但被小胶质细胞吞噬的新生或死亡细胞的数量没有性别差异。我们发现雌二醇（一种使啮齿动物大脑雄性化的激素）治疗后，雌性吞噬小胶质细胞的数量减少到雄性的典型水平。雌性海马中几个吞噬通路基因的表达也高于雄性。与吞噬性小胶质细胞存在明显的性别差异相反，我们发现具有变形虫、过渡或分支形态的小胶质细胞数量没有性别差异，小胶质细胞形态的三维重建也没有性别差异。虽然我们没有发现男性在产前性腺激素激增期间或之后小胶质细胞增殖的基线性别差异，但我们发现雌二醇治疗增加了女性小胶质细胞增殖。总之，这些数据表明，新生儿早期海马小胶质细胞功能存在重要的性别差异。
Microglia regulate brain development through many processes, such as promoting neurogenesis, supporting cell survival, and phagocytizing progenitor, newly-born, and dying cells. Many of these same developmental processes show robust sex differences, yet very few studies have assessed sex differences in microglia function during development. Hormonally-induced sexual differentiation of the brain occurs during the perinatal period, thus we examined sex differences in microglial morphology, phagocytosis, and proliferation in the hippocampus during the early postnatal period. We found that the neonatal female hippocampus had significantly more microglia with phagocytic cups than the male hippocampus. We subsequently found that female microglia phagocytized more neural progenitor cells and healthy cells compared to males, but there were no sex differences in the number of newly-born or dying cells targeted by microglial phagocytosis. We found that the number of phagocytic microglia in females was reduced to male-typical levels by treatment with estradiol, the hormone responsible for masculinizing the rodent brain. Females also had higher expression of several phagocytic pathway genes in the hippocampus compared to males. In contrast to robust sex differences in phagocytic microglia, we found no sex differences in the number of microglia with amoeboid, transitioning, or ramified morphologies or differences in three-dimensional reconstructions of microglial morphology. While we did not find a baseline sex difference in microglial proliferation during or following the prenatal gonadal hormone surge in males, we found that estradiol treatment increased microglia proliferation in females. Overall, these data show that there are important sex differences in microglia function in the hippocampus during the early neonatal period.
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DOI：
10.1523/jneurosci.4185-12.2013
发表时间：
2013-02-27
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Hodge RD;Garcia AJ 3rd;Elsen GE;Nelson BR;Mussar KE;Reiner SL;Ramirez JM;Hevner RF
通讯作者：
Hevner RF
DOI：
10.1523/jneurosci.1268-12.2013
发表时间：
2013-02-13
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Lenz KM;Nugent BM;Haliyur R;McCarthy MM
通讯作者：
McCarthy MM
影响因子：
16.6
作者：
Arno, Benedetta;Grassivaro, Francesca;Muzio, Luca
通讯作者：
Muzio, Luca
影响因子：
2.5
作者：
Ahern, Todd H.;Krug, Stefanie;Forger, Nancy G.
通讯作者：
Forger, Nancy G.
影响因子：
4.8
作者：
Konkle, Anne T. M.;McCarthy, Margaret M.
通讯作者：
McCarthy, Margaret M.