Mineralocorticoid receptor associates with pro-inflammatory bias in hippocampus of spontaneously hypertensive rats

BROCCA, MARÍA ELVIRA; PIETRANERA, LUCIANA; MEYER, MARIA; LIMA, ANALIA; ROIG, PAULINA; DE KLOET E.R.; ALEJANDRO F. DE NICOLA

JOURNAL OF NEUROENDOCRINOLOGY.

WILEY-BLACKWELL PUBLISHING, INC

Año: 2017

0953-8194

Damage observed in the hippocampus of the adult spontaneously hypertensive rat(SHR) resembles the neuropathology of mineralocorticoid-induced hypertension, supportinga similar endocrine dysfunction in both entities. In the present study, we testedthe hypothesis that increased expression of the hippocampal mineralocorticoid receptor(MR) in SHR animals is associated with a prevalent expression of pro-inflammatoryover anti-inflammatory factors. Accordingly, in the hippocampus, we measured mRNAexpression and immunoreactivity of the MR and glucocorticoid receptor (GR) using aquantitative polymerase chain reaction and histochemistry. We also measured serumglucocorticoid-activatedkinase 1 (Sgk1 mRNA), the number and phenotype of Iba1+microglia, as well as mRNA expression levels of the pro-inflammatory factors cyclooxygenase2 (Cox2), Nlrp3 inflammasome and tumour necrosis factor α (Tnfα).Expression of anti-inflammatory transforming growth factor (Tgf)β mRNA and theNADPH-diaphorase activity of nitric oxide synthase (NOS) were also determined. Theresults showed that, in the hippocampus of SHR rats, expression of MR and the numberof immunoreactive MR/GR co-expressing cells were increased compared toWistar-Kyoto control animals. Expression of Sgk1, Cox2, Nlrp3 and the number oframified glia cells positive for Iba1+ were also increased, whereas Tgfβ mRNA expressionand the NADPH-diaphorase activity of NOS were decreased. We propose that, inthe SHR hippocampus, increased MR expression causes a bias towards a proinflammatoryphenotype characteristic for hypertensive encephalopathy