Sex- and age- differences in the expression of critical blood-brain barrier regulators: a physiological context.

IF 5.1 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Xue Mi, Zi-Ling Ye, Xu-Jun Zhang, Xiao-Chun Chen, Xiao-Man Dai
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引用次数: 0

Abstract

Background: Available evidence indicates that blood-brain-barrier (BBB) dysfunction exacerbates with the advancing age and is implicated in a variety of neurological diseases and that there are significant sex differences in these diseases. However, the sex differences and age-related changes in BBB structure and function are still unclear under physiological conditions.

Methods: In this study, the mRNA was extracted from the cortical tissues and brain microvessels of male and female mice aged 3 months and 10 months to detect the expression of important BBB-related genes by qPCR.

Results: Under physiological conditions, compared with age-matched male counterparts, female mice reported a significantly lower mRNA expression of tight junction-related genes (cldn5 and occludin), transporters (Glut1 and D-gp), pericyte marker (Pdgfrb), microvessel marker (Cd31), basement membrane component (Col4a2), glycocalyx-related genes (Hs3st1, Extl2, and Clgalt), vascular homeostasis-related genes (Hif1a, Ddit4, and Pik3ca), and some regulatory genes (Adm, Zfpm2 and Nr3c1). A similar outcome was found in the 10-month mice when compared with the 3-month counterparts.

Conclusion: This study systematically analyzes the expression characteristics of key BBB regulatory genes in different sexes and ages under physiological conditions and reveals a marked sex difference in the expression of BBB structure/function-related genes, which may persist with the advancing age. The findings may provide important theoretical insights into the pathogenesis of sex-and age-related neurological diseases.

关键血脑屏障调节因子表达的性别和年龄差异:生理背景。
背景:现有证据表明,血脑屏障(BBB)功能障碍随着年龄的增长而加剧,与多种神经系统疾病有关,并且在这些疾病中存在显著的性别差异。然而,生理条件下血脑屏障结构和功能的性别差异和年龄相关变化尚不清楚。方法:本研究分别从3月龄和10月龄雄性和雌性小鼠的皮质组织和脑微血管中提取mRNA,采用qPCR检测bbb相关重要基因的表达。结果:生理条件下,与年龄匹配的雄性小鼠相比,雌性小鼠的紧密连接相关基因(cldn5和occludin)、转运体(Glut1和D-gp)、周细胞标记物(Pdgfrb)、微血管标记物(Cd31)、基膜成分(Col4a2)、糖萼相关基因(Hs3st1、Extl2和Clgalt)、血管稳态相关基因(Hif1a、Ddit4和Pik3ca)和一些调节基因(Adm、Zfpm2和Nr3c1)的mRNA表达显著降低。与3个月大的老鼠相比,10个月大的老鼠也有类似的结果。结论:本研究系统分析了血脑屏障关键调控基因在生理条件下不同性别和年龄的表达特征,揭示了血脑屏障结构/功能相关基因的表达存在显著的性别差异,且这种差异可能随着年龄的增长而持续存在。这些发现可能为性别和年龄相关的神经系统疾病的发病机制提供重要的理论见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Biology of Sex Differences
Biology of Sex Differences ENDOCRINOLOGY & METABOLISM-GENETICS & HEREDITY
CiteScore
12.10
自引率
1.30%
发文量
69
审稿时长
14 weeks
期刊介绍: Biology of Sex Differences is a unique scientific journal focusing on sex differences in physiology, behavior, and disease from molecular to phenotypic levels, incorporating both basic and clinical research. The journal aims to enhance understanding of basic principles and facilitate the development of therapeutic and diagnostic tools specific to sex differences. As an open-access journal, it is the official publication of the Organization for the Study of Sex Differences and co-published by the Society for Women's Health Research. Topical areas include, but are not limited to sex differences in: genomics; the microbiome; epigenetics; molecular and cell biology; tissue biology; physiology; interaction of tissue systems, in any system including adipose, behavioral, cardiovascular, immune, muscular, neural, renal, and skeletal; clinical studies bearing on sex differences in disease or response to therapy.
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