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A subtype of cerebrovascular pericytes is associated with blood-brain barrier disruption that develops during normal aging and simian immunodeficiency virus infection
Neurobiology of Aging ( IF 4.2 ) Pub Date : 2020-12-01 , DOI: 10.1016/j.neurobiolaging.2020.08.006
Diana G Bohannon 1 , Hamid R Okhravi 2 , Jayoung Kim 3 , Marcelo J Kuroda 4 , Elizabeth S Didier 4 , Woong-Ki Kim 1
Affiliation  

Lax phenotypic characterization of these morphologically distinct pericytes has delayed our understanding of their role in neurological disorders. We herein establish markers which uniquely distinguish different subpopulations of human brain microvascular pericytes and characterize them independently from cerebrovascular smooth muscle cells. Furthermore, we begin to elucidate the roles of these subsets in blood-brain barrier (BBB) breakdown by studying natural aging and simian immunodeficiency virus (SIV) infection in rhesus macaques. We demonstrate that the main type-1 pericyte subpopulation in the brain of young uninfected adults is positive for platelet-derived growth factor receptor-β (PDGFRB) and negative for α-smooth muscle actin (SMA) and myosin heavy chain 11 (MYH11), whereas PDGFRB+/SMA+/MYH11- (type-2) pericytes are found more frequently in older adults and are associated with SIV infection and progression. Interestingly, we find a strong positive correlation between the degree of BBB breakdown and the percentage of type-2 pericytes regardless of age or SIV status. Taken together, our findings suggest that type-2 pericytes may be a cellular biomarker related to BBB disruption independent of disease status.

中文翻译:

脑血管周细胞的一种亚型与正常衰老和猿猴免疫缺陷病毒感染期间发生的血脑屏障破坏有关

这些形态上不同的周细胞的表型特征不严格,延迟了我们对其在神经系统疾病中的作用的理解。我们在此建立了独特区分人脑微血管周细胞不同亚群的标记物,并独立于脑血管平滑肌细胞来表征它们。此外,我们通过研究恒河猴的自然衰老和猿猴免疫缺陷病毒(SIV)感染,开始阐明这些亚群在血脑屏障(BBB)破坏中的作用。我们证明,未感染的年轻人大脑中主要的 1 型周细胞亚群对血小板衍生生长因子受体-β (PDGFRB) 呈阳性,对 α-平滑肌肌动蛋白 (SMA) 和肌球蛋白重链 11 (MYH11) 呈阴性,而 PDGFRB+/SMA+/MYH11-(2 型)周细胞在老年人中更常见,并且与 SIV 感染和进展相关。有趣的是,我们发现无论年龄或 SIV 状态如何,BBB 分解程度与 2 型周细胞百分比之间存在很强的正相关性。综上所述,我们的研究结果表明,2 型周细胞可能是与 BBB 破坏相关的细胞生物标志物,与疾病状态无关。
更新日期:2020-12-01
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