GPR39 localization in the aging human brain and correlation of expression and polymorphism with vascular cognitive impairment.
GPR39 localization in the aging human brain and correlation of expression and polymorphism with vascular cognitive impairment.
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DOI：
10.1002/trc2.12214
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Alkayed NJ
中科院分区：
文献类型：
--
作者：
Davis CM;Bah TM;Zhang WH;Nelson JW;Golgotiu K;Nie X;Alkayed FN;Young JM;Woltjer RL;Silbert LC;Grafe MR;Alkayed NJ
血管性认知障碍（VCI）的发病机制尚未完全清楚。GPR 39是一种孤儿G蛋白偶联受体，与神经系统疾病有关，但其在VCI中的作用尚不清楚。我们对轻度认知障碍（MCI）和对照组的死后脑组织样本进行了GPR 39免疫组化分析。分析DNA中GPR 39单核苷酸多态性（SNP），并与死前磁共振成像上的白色高信号（WMH）负荷相关。GPR 39在老年人背外侧前额叶皮层中表达，定位于小胶质细胞和类似周细胞的微血管细胞。GPR 39-毛细血管共定位和GPR 39-表达小胶质细胞的密度在老年脑中比年轻脑中增加。SNP分布在组间是相等的;然而，纯合SNP携带者仅存在于MCI组中，并且具有比野生型或杂合SNP携带者更高的WMH体积。GPR 39可能在衰老相关的VCI中发挥作用，并可能作为发展VCI风险的治疗靶点和生物标志物。
The pathogenesis of vascular cognitive impairment (VCI) is not fully understood. GPR39, an orphan G‐protein coupled receptor, is implicated in neurological disorders but its role in VCI is unknown. We performed GPR39 immunohistochemical analysis in post mortem brain samples from mild cognitive impairment (MCI) and control subjects. DNA was analyzed for GPR39 single nucleotide polymorphisms (SNPs), and correlated with white matter hyperintensity (WMH) burden on pre mortem magnetic resonance imaging. GPR39 is expressed in aged human dorsolateral prefrontal cortex, localized to microglia and peri‐capillary cells resembling pericytes. GPR39–capillary colocalization, and density of GPR39‐expressing microglia was increased in aged brains compared to young. SNP distribution was equivalent between groups; however, homozygous SNP carriers were present only in the MCI group, and had higher WMH volume than wild‐type or heterozygous SNP carriers. GPR39 may play a role in aging‐related VCI, and may serve as a therapeutic target and biomarker for the risk of developing VCI.
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