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

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

doi:10.1002/trc2.12214

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

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

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14 Scopus citations

Abstract

Introduction: 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. 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. 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.

Original language	English (US)
Article number	e12214
Journal	Alzheimer's and Dementia: Translational Research and Clinical Interventions
Volume	7
Issue number	1
DOIs	https://doi.org/10.1002/trc2.12214
State	Published - 2021

ASJC Scopus subject areas

Clinical Neurology
Psychiatry and Mental health

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Davis, C. M., Bah, T. M., Zhang, W. H., Nelson, J. W., Golgotiu, K., Nie, X., Alkayed, F. N., Young, J. M., Woltjer, R. L., Silbert, L. C., Grafe, M. R., & Alkayed, N. J. (2021). GPR39 localization in the aging human brain and correlation of expression and polymorphism with vascular cognitive impairment. Alzheimer's and Dementia: Translational Research and Clinical Interventions, 7(1), Article e12214. https://doi.org/10.1002/trc2.12214

Davis, CM, Bah, TM, Zhang, WH, Nelson, JW, Golgotiu, K, Nie, X, Alkayed, FN, Young, JM, Woltjer, RL , Silbert, LC, Grafe, MR & Alkayed, NJ 2021, 'GPR39 localization in the aging human brain and correlation of expression and polymorphism with vascular cognitive impairment', Alzheimer's and Dementia: Translational Research and Clinical Interventions, vol. 7, no. 1, e12214. https://doi.org/10.1002/trc2.12214

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abstract = "Introduction: 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. 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. 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.",

author = "Davis, {Catherine M.} and Bah, {Thierno M.} and Zhang, {Wenri H.} and Nelson, {Jonathan W.} and Kirsti Golgotiu and Xiao Nie and Alkayed, {Farah N.} and Young, {Jennifer M.} and Woltjer, {Randy L.} and Silbert, {Lisa C.} and Grafe, {Marjorie R.} and Alkayed, {Nabil J.}",

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year = "2021",

doi = "10.1002/trc2.12214",

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AU - Davis, Catherine M.

AU - Bah, Thierno M.

AU - Zhang, Wenri H.

AU - Nelson, Jonathan W.

AU - Golgotiu, Kirsti

AU - Nie, Xiao

AU - Alkayed, Farah N.

AU - Young, Jennifer M.

AU - Woltjer, Randy L.

AU - Silbert, Lisa C.

AU - Grafe, Marjorie R.

AU - Alkayed, Nabil J.

PY - 2021

Y1 - 2021

N2 - Introduction: 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. 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. 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.

AB - Introduction: 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. 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. 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.

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

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