Selective oestrogen receptor agonists rescued hippocampus parameters in male spontaneously hypertensive rats

Spontaneously hypertensive rats (SHR) show pronounced hippocampus alterations, including low brain derived neurotropic factor expression, reduced neurogenesis, astrogliosis and increased aromatase expression. These changes are reverted by treatment with 17β-oestradiol. To elucidate which oestradiol receptor (ER) type is involved in these neuroprotective effects, we used agonists of the ERα (propylpyrazole triol,PPT) and the ERβ (diarylpropionitrite, DPN) given during 2 weeks to 4 month old male SHR. Wistar Kyoto (WKY) normotensive rats served as controls. Using immunocytochemistry, we determined glial fibrillary protein (GFAP)+ astrocytes in the CA1, CA3 and hilus of the dentate gyrus of hippocampus, aromatase immunostaining in the hilus and doublecortin (DCX) + neuronal progenitors in the inner granular zone of the dentate gyrus. BDNF mRNA was also measured in hippocampus by qPCR. The results showed that PPT had no effect on blood pressure of SHR, decreased astrogliosis, and increased aromatase staining, slightly increased BDNF mRNA but had no effect on the number of DCX+ progenitors. Treatment with DPN decreased blood pressure of SHR, decreased astrogliosis, increased BDNF mRNA and DCX+ progenitors but did not modify aromatase staining. We hypothesize that while both receptor types may participate in the previously reported beneficial effects of 17β-oestradiol in SHR, receptor activation with DPN may preferentially facilitate BDNF mRNA expression and neurogenesis. This study may help to design ER-based neuroprotection for the encephalopathy of hypertension. This article is protected by copyright. All rights reserved.