Microglia in the RVLM of SHR have reduced P2Y12R and CX3CR1 expression, shorter processes, and lower cell density

E Myfanwy Cohen; Suja Mohammed; Mary Kavurma; Polina E Nedoboy; Siân Cartland; Melissa M J Farnham; Paul M Pilowsky

doi:10.1016/j.autneu.2018.12.002

Microglia in the RVLM of SHR have reduced P2Y12R and CX3CR1 expression, shorter processes, and lower cell density

Auton Neurosci. 2019 Jan:216:9-16. doi: 10.1016/j.autneu.2018.12.002. Epub 2018 Dec 8.

Authors

E Myfanwy Cohen¹, Suja Mohammed¹, Mary Kavurma¹, Polina E Nedoboy¹, Siân Cartland¹, Melissa M J Farnham¹, Paul M Pilowsky²

Affiliations

¹ The Heart Research Institute, Sydney, New South Wales 2042, Australia; Sydney Medical School, University of Sydney, Sydney, New South Wales 2006, Australia.
² The Heart Research Institute, Sydney, New South Wales 2042, Australia; Sydney Medical School, University of Sydney, Sydney, New South Wales 2006, Australia. Electronic address: paul.pilowsky@sydney.edu.au.

PMID: 30598122
DOI: 10.1016/j.autneu.2018.12.002

Abstract

The RVLM of spontaneously hypertensive rats (SHR) contains over-active C1 neurons, which model the pathology of essential hypertension. Hypertension involves chronic low-grade neuroinflammation. Inflammation in the brain is produced and maintained primarily by microglia. We assessed microglial gene expression (P2Y12R and CX3CR1) and morphology in the RVLM of SHR compared to normotensive Wistar-Kyoto rats (WKY). The gene expression of the metabotropic purinergic receptor P2Y12 and the fractalkine receptor CX3CR1 was downregulated in the RVLM of SHR compared to WKY (by 37.3% and 30.9% respectively). P2Y12R and CX3CR1 are required for normal microglial function, and reduced P2Y12R expression is associated with changes in microglial activity. Histological analysis showed a 22.9% reduction in microglial cell density, along with 18.7% shorter microglial processes, a phenotypic indicator of activation, in the RVLM of SHR compared to WKY. These results indicate a subtle loss of function, or a mild state of inflammation, in the RVLM microglia of SHR.

Keywords: CX3CR1; Hypertension; Microglia; P2Y12R; RVLM; SHR.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
CX3C Chemokine Receptor 1 / biosynthesis*
Cell Count
Down-Regulation
Gene Expression / physiology
Male
Medulla Oblongata / cytology*
Medulla Oblongata / metabolism
Microglia / cytology*
Microglia / metabolism*
Rats
Rats, Inbred SHR
Rats, Inbred WKY
Receptors, Purinergic P2Y12 / biosynthesis*
Species Specificity

Substances

CX3C Chemokine Receptor 1
CX3CR1 protein, rat
Receptors, Purinergic P2Y12