GPR39 localization in the aging human brain and correlation of expression and polymorphism with vascular cognitive impairment
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 sam...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Alzheimer’s & Dementia: Translational Research & Clinical Interventions |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/trc2.12214 |
| _version_ | 1828134572551831552 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Catherine M. Davis |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T17:36:27Z |
| format | Article |
| id | doaj.art-4d536f292a5248eaa224b392eaaa42b2 |
| institution | Directory Open Access Journal |
| issn | 2352-8737 |
| language | English |
| last_indexed | 2024-04-11T17:36:27Z |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Alzheimer’s & Dementia: Translational Research & Clinical Interventions |
| spelling | doaj.art-4d536f292a5248eaa224b392eaaa42b22022-12-22T04:11:35ZengWileyAlzheimer’s & Dementia: Translational Research & Clinical Interventions2352-87372021-01-0171n/an/a10.1002/trc2.12214GPR39 localization in the aging human brain and correlation of expression and polymorphism with vascular cognitive impairmentCatherine M. Davis0Thierno M. Bah1Wenri H. Zhang2Jonathan W. Nelson3Kirsti Golgotiu4Xiao Nie5Farah N. Alkayed6Jennifer M. Young7Randy L. Woltjer8Lisa C. Silbert9Marjorie R. Grafe10Nabil J. Alkayed11Department of Anesthesiology & Perioperative Medicine Oregon Health & Science University Portland Oregon USADepartment of Anesthesiology & Perioperative Medicine Oregon Health & Science University Portland Oregon USADepartment of Anesthesiology & Perioperative Medicine Oregon Health & Science University Portland Oregon USADivision of Nephrology and Hypertension, Department of Medicine Oregon Health & Science University Portland Oregon USADepartment of Anesthesiology & Perioperative Medicine Oregon Health & Science University Portland Oregon USADepartment of Anesthesiology & Perioperative Medicine Oregon Health & Science University Portland Oregon USADepartment of Anesthesiology & Perioperative Medicine Oregon Health & Science University Portland Oregon USADepartment of Anesthesiology & Perioperative Medicine Oregon Health & Science University Portland Oregon USADepartment of Pathology Oregon Health & Science University Portland Oregon USALayton Aging and Alzheimer's Disease Research Center Department of Neurology Oregon Health & Science University Portland Oregon USADepartment of Anesthesiology & Perioperative Medicine Oregon Health & Science University Portland Oregon USADepartment of Anesthesiology & Perioperative Medicine Oregon Health & Science University Portland Oregon USAAbstract 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.https://doi.org/10.1002/trc2.12214GPR39microgliamild cognitive impairmentpolymorphismvascular cognitive impairmentwhite matter hyperintensity |
| spellingShingle | 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 GPR39 localization in the aging human brain and correlation of expression and polymorphism with vascular cognitive impairment Alzheimer’s & Dementia: Translational Research & Clinical Interventions GPR39 microglia mild cognitive impairment polymorphism vascular cognitive impairment white matter hyperintensity |
| title | GPR39 localization in the aging human brain and correlation of expression and polymorphism with vascular cognitive impairment |
| title_full | GPR39 localization in the aging human brain and correlation of expression and polymorphism with vascular cognitive impairment |
| title_fullStr | GPR39 localization in the aging human brain and correlation of expression and polymorphism with vascular cognitive impairment |
| title_full_unstemmed | GPR39 localization in the aging human brain and correlation of expression and polymorphism with vascular cognitive impairment |
| title_short | GPR39 localization in the aging human brain and correlation of expression and polymorphism with vascular cognitive impairment |
| title_sort | gpr39 localization in the aging human brain and correlation of expression and polymorphism with vascular cognitive impairment |
| topic | GPR39 microglia mild cognitive impairment polymorphism vascular cognitive impairment white matter hyperintensity |
| url | https://doi.org/10.1002/trc2.12214 |
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