Sex differences in prefrontal cortex microglia morphology: Impact of a two-hit model of adversity throughout development.
Sex differences in prefrontal cortex microglia morphology: Impact of a two-hit model of adversity throughout development.
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DOI：
10.1016/j.neulet.2020.135381
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发表时间：
2020-11-01
影响因子：
2.5
通讯作者：
Brenhouse HC
中科院分区：
文献类型：
--
作者：
Gildawie KR;Orso R;Peterzell S;Thompson V;Brenhouse HC
神经免疫机制在大脑发育中起着关键作用，并可能受到早期生活逆境的影响。小胶质细胞是大脑中的常驻免疫细胞，具有性别特异性和区域特异性的发育概况。由于早期生活逆境与几种具有发育发病机制的神经精神疾病有关，我们在这里研究了母体分离（MS）对小胶质细胞发育的影响程度。小胶质细胞是一种动态细胞，根据其功能和对应激源的反应改变其形态。据报道，在发育过程中，在免疫和心理挑战之后，男性和女性在几个大脑区域显示出不同的小胶质细胞形态，但对前额叶皮层（PFC）的这种差异知之甚少，而前额叶皮层调节着几种早期生活逆境导致的疾病。此外，人们对早期生活逆境对小胶质细胞日后免疫挑战的潜在影响知之甚少。在本研究中，雄性和雌性大鼠在幼年或青春期暴露于MS后再给予脂多糖。然后分别分析边缘前和边缘下PFC的小胶质细胞密度和形态。典型发育中的雄性在幼年时比雌性表达较小的躯体和较少的乔木化，但在青春期比雌性表达较大的躯体。多发性硬化症导致青春期男性边缘下PFC小胶质细胞减少。质谱和脂多糖处理都会影响雄性和雌性幼鱼的形态特征，其中质谱暴露导致脂多糖处理后体细胞大小增加更大。有趣的是，MS和脂多糖的影响在青春期未被观察到，而PFC小胶质细胞形态的显著性别差异是明显的。综上所述，这些发现为PFC小胶质细胞如何对男性和女性的发育挑战做出不同的反应提供了见解。
Neuroimmune mechanisms play critical roles in brain development and can be impacted by early life adversity. Microglia are the resident immune cells in the brain, with both sex-specific and region-specific developmental profiles. Since early life adversity is associated with several neuropsychiatric disorders with developmental pathogeneses, here we investigated the degree to which maternal separation (MS) impacted microglia over development. Microglia are dynamic cells that alter their morphology in accordance with their functions and in response to stressors. While males and females reportedly display different microglial morphology in several brain regions over development and following immune and psychological challenges, little is known about such differences in the prefrontal cortex (PFC), which regulates several early life adversity-attributable disorders. Additionally, little is known about the potential for early life adversity to prime microglia for later immune challenges. In the current study, male and female rats were exposed to MS followed by lipopolysaccharide administration in juvenility or adolescence. The prelimbic and infralimbic PFC were then separately analyzed for microglial density and morphology. Typically developing males expressed smaller soma and less arborization than females in juvenility, but larger soma than females in adolescence. MS led to fewer microglia in the infralimbic PFC of adolescent males. Both MS and lipopolysaccharide administration affected morphological characteristics in juvenile males and females, with MS exposure leading to a greater increase in soma size following lipopolysaccharide. Interestingly, effects of MS and lipopolysaccharide were not observed in adolescence, while notable sex differences in PFC microglial morphology were apparent. Taken together, these findings provide insight into how PFC microglia may differentially respond to challenges over development in males and females.
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影响因子：
34.7
作者：
Arnsten, Amy F. T.
通讯作者：
Arnsten, Amy F. T.
影响因子：
4.2
作者：
Buttini, M;Limonta, S;Boddeke, HWGM
通讯作者：
Boddeke, HWGM
影响因子：
3.4
作者：
Fishkin, RJ;Winslow, JT
通讯作者：
Winslow, JT
影响因子：
15.1
作者：
Delpech, Jean-Christophe;Wei, Lan;Hao, Jin;Yu, Xiaoqing;Madore, Charlotte;Butovsky, Oleg;Kaffman, Arie
通讯作者：
Kaffman, Arie
影响因子：
6.2
作者：
Bilbo, Staci D.;Smith, Susan H.;Schwarz, Jaclyn M.
通讯作者：
Schwarz, Jaclyn M.