Mineralocorticoid receptor (MR) and neuroinflammation in the hippocampus of spontaneously hypertensive rats (SHR)

M.E. BROCCA; A. LIMA; L. PIETRANERA; A.F. DE NICOLA; N. PILONI; P. ROIG

Buenos Aires

Congreso; 2nd FALAN Congress; 2016

SHR show increased MR mRNA in hippocampus (HC), suggesting a dysfunctional endocrine system. We investigatedif abnormalities of MR are associated with neuroinflammation in the HC of SHR.10 month old male SHR (BP: 185 mm Hg) and normotensive WKY rats were sacrificedand brains removed to study 1) MR and GR co-expression 2) microglia phenotypeand 3) proinflammatory markers. SHR showed higher levels of MR mRNA in whole HCand higher number of MR+ cells/mm2 in the CA3 region (p<0.01 vs WKY). The %of MR+ cells that co-express GR in HC was higher in SHR than in WKY in CA1 andCA3 regions (p<0.05). SHR also showed higher number of ramified hypertrophicmicroglia in the CA1 region, higher number of ramified and lower number ofround microglia in the CA3 region (p<0.05 vs WKY). MR functional activity,determined by serum- and glucocorticoid-inducible kinase 1 (sgk1) mRNA levels,was higher in SHR (p<0.01 vs WKY). COX2 mRNA levels were increased in the HCof SHR vs WKY rats (p<0.05). However, mRNAs for the inflammasome componentNLRP3 and the IKb alpha inhibitor of NFkB were not modified in SHR vs WKY rats.Our data indicated region specificity in the response of MR and itscolocalisation with GR in the HC of SHR. SHR showed evidence of modifiedmicroglia phenotypes in CA1 and CA3 regions and high COX2 mRNA expression.Thus, changes of MR mRNA and protein may trigger the enhanced expression of theinflammatory factor sgk1 suggesting a neurotoxic role of MR overexpression.