GPR39 localization in the aging human brain and correlation of expression and polymorphism with vascular cognitive impairment

GPR39 在衰老人类脑中的定位以及表达和多态性与血管性认知障碍的相关性

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作者:Catherine M Davis, Thierno M Bah, Wenri H Zhang, Jonathan W Nelson, Kirsti Golgotiu, Xiao Nie, Farah N Alkayed, Jennifer M Young, Randy L Woltjer, Lisa C Silbert, Marjorie R Grafe, Nabil J Alkayed

Discussion

GPR39 may play a role in aging-related VCI, and may serve as a therapeutic target and biomarker for the risk of developing VCI.

Methods

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.

Results

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.

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