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Research Article| Volume 216, P9-16, January 2019

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

Published:December 08, 2018DOI:https://doi.org/10.1016/j.autneu.2018.12.002

      Highlights

      • Hypertension is associated with neuroinflammation and RVLM neuron over-activity
      • Neuroinflammation is produced and maintained primarily by microglia
      • Changes in microglial phenotype and morphology can affect neuronal function
      • We found RVLM-specific changes in microglial gene expression and morphology

      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.

      Abbreviations:

      RVLM (rostral ventrolateral medulla), SHR (spontaneously hypertensive rat), WKY (Wistar-Kyoto rat), CNS (central nervous system), PFA (paraformaldehyde), SBP (systolic blood pressure), LPS (lipopolysaccharide)

      Keywords

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