Resilience to stress and sex-specific remodeling of microglia and neuronal morphology in a rat model of anxiety and anhedonia.
Resilience to stress and sex-specific remodeling of microglia and neuronal morphology in a rat model of anxiety and anhedonia.
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DOI：
10.1016/j.ynstr.2021.100302
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发表时间：
2021-05
影响因子：
5
通讯作者：
Gomes CA
中科院分区：
文献类型：
--
作者：
Gaspar R;Soares-Cunha C;Domingues AV;Coimbra B;Baptista FI;Pinto L;Ambrósio AF;Rodrigues AJ;Gomes CA
产前暴露于压力或糖皮质激素（GC）与以后生活中精神疾病的出现有关。小胶质细胞，大脑的免疫细胞，在与压力有关的疾病中发生改变。合成GC如地塞米松（DEX）通常用于早产风险分娩，以促进胎儿肺成熟。最近，我们报道了子宫内暴露于DEX（iuDEX）的模型中小胶质细胞形态的长期差异，该模型呈现焦虑表型。然而，目前尚不清楚压力是否对iuDEX男性和女性产生不同影响。在这项工作中，我们评估了两种性别的iuDEX动物如何科普2周的慢性轻度应激。我们评估了情绪行为和小胶质细胞和神经元形态的背海马（dHIP）和脑桥核（NAc），两个大脑区域参与情绪相关的疾病。我们报告说，男性和女性产前暴露于DEX有更好的表现在焦虑和抑郁相关的行为测试后，慢性压力暴露在成年期比非暴露的动物。有趣的是，iuDEX动物在dHIP（雌性肥大）和NAc（雌性萎缩和雄性肥大）中的小胶质细胞形态中呈现性别依赖性变化。在慢性应激后，这些细胞进行性别特异性的形态重塑。在小胶质细胞的细胞结构的这些改变，我们报告的树突状形态的性别特异性的方式区域间的差异。iuDEX雌性在NAc中呈现较少的复杂神经元，而iuDEX雄性在dHIP中呈现较少的复杂神经元形态。有趣的是，这些改变被压力暴露所改变。我们的工作表明，怀孕期间的压力事件可以在成年后产生保留的性别特异性影响。虽然所观察到的细胞重塑的作用仍然是未知的，性别特异性差异小胶质细胞的可塑性诱导的长期压力暴露可能会预期在压力诱导的焦虑或抑郁相关行为的背景下，药物疗效的差异。iuDEX在两种性别中诱导焦虑和抑郁相关行为。iuDEX诱导dHIP和NAc中神经元和小胶质细胞形态的性别依赖性精细结构改变。uCMS与iuDEX的组合使NAc中神经元的行为以及形态正常化。怀孕期间的压力事件可以在成年后产生保留的性别特异性影响。
Prenatal exposure to stress or glucocorticoids (GC) is associated with the appearance of psychiatric diseases later in life. Microglia, the immune cells of the brain, are altered in stress-related disorders. Synthetic GC such as dexamethasone (DEX) are commonly prescribed in case of preterm risk labour in order to promote fetal lung maturation. Recently, we reported long-lasting differences in microglia morphology in a model of in utero exposure to DEX (iuDEX), that presents an anxious phenotype. However, it is still unclear if stress differentially affects iuDEX males and females. In this work, we evaluated how iuDEX animals of both sexes cope with chronic mild stress for 2 weeks. We evaluated emotional behavior and microglia and neuronal morphology in the dorsal hippocampus (dHIP) and nucleus accumbens (NAc), two brain regions involved in emotion-related disorders. We report that males and females prenatally exposed to DEX have better performance in anxiety- and depression-related behavioral tests after chronic stress exposure in adulthood than non-exposed animals. Interestingly, iuDEX animals present sex-dependent changes in microglia morphology in the dHIP (hypertrophy in females) and in the NAc (atrophy in females and hypertrophy in males). After chronic stress, these cells undergo sex-specific morphological remodeling. Paralleled to these alterations in cytoarchitecture of microglia, we report inter-regional differences in dendritic morphology in a sex-specific manner. iuDEX females present fewer complex neurons in the NAc, whereas iuDEX males presented less complex neuronal morphology in the dHIP. Interestingly, these alterations were modified by stress exposure. Our work shows that stressful events during pregnancy can exert a preserved sex-specific effect in adulthood. Although the role of the observed cellular remodeling is still unknown, sex-specific differences in microglia plasticity induced by long-term stress exposure may anticipate differences in drug efficacy in the context of stress-induced anxiety- or depression-related behaviors. iuDEX induces anxiety- and depression-related behavioral in both sexes. iuDEX induces sex dependent fine structural alterations in neurons and microglia morphology in the dHIP and in the NAc. uCMS in combination to iuDEX normalize the behavior as well the morphology of neurons in the NAc. Stressful events during pregnancy can exert a preserved sex-specific effect in adulthood.
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影响因子：
16.2
作者：
Fanselow, Michael S.;Dong, Hong-Wei
通讯作者：
Dong, Hong-Wei
影响因子：
11
作者：
Bessa, J. M.;Ferreira, D.;Sousa, N.
通讯作者：
Sousa, N.
影响因子：
6.2
作者：
Duarte, Joana Mendes;Gaspar, Rita;Gomes, Catarina A.
通讯作者：
Gomes, Catarina A.
影响因子：
5.3
作者：
Cristovão G;Pinto MJ;Cunha RA;Almeida RD;Gomes CA
通讯作者：
Gomes CA
影响因子：
5.6
作者：
Pinheiro H;Gaspar R;Baptista FI;Fontes-Ribeiro CA;Ambrósio AF;Gomes CA
通讯作者：
Gomes CA