Peri-Infarct Upregulation of the Oxytocin Receptor in Vascular Dementia.

Abstract:

:Vascular dementia (VaD) is cognitive decline linked to reduced cerebral blood perfusion, yet there are few therapeutic options to protect cognitive function following cerebrovascular accidents. The purpose of this study was to profile gene expression changes unique to VaD to identify and characterize disease relevant changes that could offer clues for future therapeutic direction. Microarray-based profiling and validation studies of postmortem frontal cortex samples from VaD, Alzheimer disease, and age-matched control subjects revealed that the oxytocin receptor (OXTR) was strongly and differentially upregulated in VaD. Further characterization in fixed tissue from the same cases showed that OXTR upregulation occurs de novo around and within microinfarcts in peri-infarct reactive astrocytes as well as within vascular profiles, likely on microvascular endothelial cells. These results indicate that increased OXTR expression in peri-infarct regions may be a specific response to microvascular insults. Given the established OXTR signaling cascades that elicit antioxidant, anti-inflammatory, and pro-angiogenic responses, the present findings suggest that de novo OXTR expression in the peri-infarct space is a tissue-protective response by astroglial and vascular cells in the wake of ischemic damage that could be exploited as a therapeutic option for the preservation of cognition following cerebrovascular insults.

authors

McKay EC,Beck JS,Khoo SK,Dykema KJ,Cottingham SL,Winn ME,Paulson HL,Lieberman AP,Counts SE

doi

10.1093/jnen/nlz023

subject

Has Abstract

pub_date

2019-05-01 00:00:00

pages

436-452

issue

5

eissn

0022-3069

issn

1554-6578

pii

5445920

journal_volume

78

pub_type

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