染色体和性腺因素调节衰老大脑中小胶质细胞的性别效应。
Chromosomal and gonadal factors regulate microglial sex effects in the aging brain.
机构信息
Genes & Human Disease Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA; Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Genes & Human Disease Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA; Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
出版信息
Brain Res Bull. 2023 Apr;195:157-171. doi: 10.1016/j.brainresbull.2023.02.008. Epub 2023 Feb 15.
Biological sex contributes to phenotypic sex effects through genetic (sex chromosomal) and hormonal (gonadal) mechanisms. There are profound sex differences in the prevalence and progression of age-related brain diseases, including neurodegenerative diseases. Inflammation of neural tissue is one of the most consistent age-related phenotypes seen with healthy aging and disease. The pro-inflammatory environment of the aging brain has primarily been attributed to microglial reactivity and adoption of heterogeneous reactive states dependent upon intrinsic (i.e., sex) and extrinsic (i.e., age, disease state) factors. Here, we review sex effects in microglia across the lifespan, explore potential genetic and hormonal molecular mechanisms of microglial sex effects, and discuss currently available models and methods to study sex effects in the aging brain. Despite recent attention to this area, significant further research is needed to mechanistically understand the regulation of microglial sex effects across the lifespan, which may open new avenues for sex informed prevention and treatment strategies.
生物性别通过遗传（性染色体）和激素（性腺）机制对表型性别效应产生影响。与年龄相关的脑部疾病（包括神经退行性疾病）的患病率和进展在性别上存在显著差异。神经组织的炎症是健康衰老和疾病中最常见的与年龄相关表型之一。衰老大脑的促炎环境主要归因于小胶质细胞的反应性以及依赖于内在（即性别）和外在（即年龄、疾病状态）因素的异质反应状态。在这里，我们综述了小胶质细胞在整个生命周期中的性别效应，探讨了小胶质细胞性别效应的潜在遗传和激素分子机制，并讨论了目前用于研究衰老大脑中性别效应的模型和方法。尽管最近人们对这一领域的关注度有所提高，但仍需要进一步的研究来从机制上理解小胶质细胞性别效应在整个生命周期中的调节，这可能为基于性别的预防和治疗策略开辟新途径。
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