Sex differences in astrocyte and microglia responses immediately following middle cerebral artery occlusion in adult mice.
Sex differences in astrocyte and microglia responses immediately following middle cerebral artery occlusion in adult mice.
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DOI：
10.1016/j.neuroscience.2016.09.047
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发表时间：
2016-12-17
期刊：
影响因子：
3.3
通讯作者：
Filosa JA
中科院分区：
文献类型：
--
作者：
Morrison HW;Filosa JA
流行病学研究报告说，与男性相比，年轻女性的脑梗塞面积缩小，中风结果得到改善。然而，缺乏机械性的洞察力。我们假设在缺血性卒中后立即出现的神经胶质细胞功能的性别差异是二分性结果的一个来源。在本研究中，我们观察了雄性和雌性小鼠大脑中动脉闭塞60分钟后星形胶质细胞的钙动力学、水通道蛋白4的极性、S100β的表达模式以及小胶质细胞的形态和吞噬标记CD11b。急性脑片缺血后即刻星形胶质细胞内钙升高的频率(F(1，86)=8.19，P=0.005)和小胶质细胞体积(F(1，40)=12.47，P=0.009)存在性别差异。在固定组织中测量，大脑中动脉闭塞60min后，同侧脑区AQP4极性被破坏(F(5，86)=3.3，P=0.009)，非S100β免疫反应阳性区面积增加(F(5，86)=4.72，P=0.007)。然而，与雌性小鼠相比，雄性小鼠的星形胶质细胞变化更明显。此外，还发现了小胶质细胞吞噬细胞受体CD11b的性别差异。在假手术组，雌性小鼠的CD11b免疫荧光高于雄性小鼠(P=0.03)。与假手术组相比，仅雄性小鼠大脑中动脉结扎后CD11b免疫反应增强(P=0.006)。我们假设，在存在结构性CD11b的情况下，性别差异在决定男性和女性小胶质细胞对缺血的吞噬反应中具有作用。综上所述，这些发现对于理解神经胶质生理学和中风病理生物学中潜在的性别差异至关重要，这是未来针对性别的中风治疗方法发展的基础。
Epidemiological studies report that infarct size is decreased and stroke outcomes are improved in young females when compared to males. However, mechanistic insight is lacking. We posit that sex-specific differences in glial cell functions occurring immediately after ischemic stroke are a source of dichotomous outcomes. In this study we assessed astrocyte Ca2+ dynamics, aquaporin 4 (AQP4) polarity, S100β expression pattern, as well as, microglia morphology and phagocytic marker CD11b in male and female mice following 60 minutes of middle cerebral artery (MCA) occlusion. We reveal sex differences in the frequency of intracellular astrocyte Ca2+ elevations (F(1,86)=8.19, P=0.005) and microglia volume (F(1,40)=12.47, P=0.009) immediately following MCA occlusion in acute brain slices. Measured in fixed tissue, AQP4 polarity was disrupted (F(5,86)=3.30, P=0.009) and the area of non-S100β immunoreactivity increased in ipsilateral brain regions after 60 min of MCA occlusion (F(5,86)=4.72, P=0.007). However, astrocyte changes were robust in male mice when compared to females. Additional sex differences were discovered regarding microglia phagocytic receptor CD11b. In sham mice, constitutively high CD11b immunofluorescence was observed in females when compared to males (P=0.03). When compared to sham, only male mice exhibited an increase in CD11b immunoreactivity after MCA occlusion (P=0.006). We posit that a sex difference in the presence of constitutive CD11b has a role in determining male and female microglia phagocytic responses to ischemia. Taken together, these findings are critical to understanding potential sex differences in glial physiology as well as stroke pathobiology which are foundational for the development of future sex-specific stroke therapies.