Chromosomal and gonadal factors regulate microglial sex effects in the aging brain

被引:8
作者
Ocanas, Sarah R. [1 ,2 ]
Ansere, Victor A. [1 ,2 ]
Kellogg, Collyn M. [1 ,5 ]
Isola, Jose V. V. [3 ]
Chucair-Elliott, Ana J. [1 ]
Freeman, Willard M. [1 ,4 ,5 ]
机构
[1] Oklahoma Med Res Fdn, Genes & Human Dis Program, 825 NE 13th St, Oklahoma City, OK 73104 USA
[2] Univ Oklahoma, Dept Physiol, Hlth Sci Ctr, Oklahoma City, OK USA
[3] Oklahoma Med Res Fdn, Aging & Metab Program, Oklahoma City, OK USA
[4] Oklahoma City Vet Affairs Med Ctr, Oklahoma City, OK USA
[5] Univ Oklahoma, Dept Biochem & Mol Biol, Hlth Sci Ctr, Oklahoma City, OK USA
基金
美国国家卫生研究院;
关键词
Microglia; Sex difference; Neuroimmune; Sex chromosome; Aging; Sex hormones; Estrogen; X-chromosome inactivation; CENTRAL-NERVOUS-SYSTEM; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; ESTROGEN REPLACEMENT THERAPY; MILD COGNITIVE IMPAIRMENT; CORONARY-HEART-DISEASE; X-CHROMOSOME; POSTMENOPAUSAL WOMEN; MOSAIC LOSS; ALZHEIMERS-DISEASE; FREE TESTOSTERONE;
D O I
10.1016/j.brainresbull.2023.02.008
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:157 / 171
页数:15
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