Increased aromatse expression in the hippocampus of spontaneuously hypertensive rats: effects of estradiol administration

PIETRANERA, LUCIANA; BELLINI, M. JOSÉ; ARÉVALO, M. ANGELES; GOYA, RODOLFO; BROCCA, M. ELVIRA; GARCIA SEGURA, LUIS MIGUEL; DE NICOLA, ALEJANDRO F.

NEUROSCIENCE

PERGAMON-ELSEVIER SCIENCE LTD

Año: 2011 vol. 174 p. 151 - 159

0306-4522

There is high incidence of hippocampal abnormalities in spontaneously hypertensive rats (SHR), including decreased neurogenesis in the dentate gyrus, astrogliosis, low expression of brain derived neurotrophic factor and decreased neuronal density in the hilar region, respect of normotensive Wistar Kyoto rats (WKY). Estradiol treatment given for 2 weeks normalized the faulty hippocampal parameters of SHR, without having effects on WKY rats. The present work studied the potential role of local estrogen biosynthesis in SHR and WKY, by measuring the expression of aromatase, the key enzyme responsible for estrogen biosynthesis and involved in neuroprotection. We used 4 month old male SHR and WKY, half of which received sc a single estradiol benzoate pellet weighing 12 mg and the remaining half a cholesterol implant. Hippocampi were dissected and processed for aromatase mRNA expression using real time PCR; whereas a second batch of animals was processed for aromatase and glial fibrillary acidic protein (GFAP) immunocytochemistry. Basal levels of aromatase mRNA were higher in SHR respect of WKY. Following estradiol treatment, aromatase mRNA was further increased in the SHR group only. Aromatase immunoreactive cell processes and fibers in the hilus of the dentate gyrus of steroid-untreated SHR were more strongly stained than those of WKY rats. Estradiol treatment further increased the length of immunoreactive processes and fibers in the hilar region and also increased aromatase immunoreaction intensity of pyramidal CA1 neurons of SHR but not WKY rats. Double-labelling experiments showed that aromatase+ processes and fibers of the hilus did no colocalize with GFAP+ astrocyte bodies or processes. In conclusion, basal and estradiol-stimulated aromatase expression was enhanced in hypertensive rat hippocampus. A combination of exogenous estrogens and those locally synthesized may better alleviate hypertensive encephalopathy.