Protective effects of estrogens on the brain of rats with essential and endocrine hypertension

DE NICOLA A.F.; PIETRANERA L.; BELLINI M.J.; GOYA R.; BROCCA M.E.; GARCIA-SEGURA L.M:

Hormone Molecular Biology and Clinical Investigation

de Gruyter

Lugar: Berlin; Año: 2010 vol. 4 p. 549 - 558

1868-1883

Estrogen neuroprotection has been demonstrated in several pathological conditions such as brain injury, aging and neurodegenerative diseases. Hypertension is known to cause a pronounced encephalopathy, targeting among other areas the hippocampal formation; therefore, hypertension seems an appropriate situation to study estrogen neuroprotection. In this regard, the hippocampus of spontaneously hypertensive rats (SHR) and deoxycorticosterone (DOCA)-salt hypertensive rats share several abnormalities, including decreased neurogenesis in the dentate gyrus, astrogliosis, low expression of brain derived neurotrophic factor (BDNF) and decreased number of neurons in the hilar region, with respect to their normotensive strains Wistar Kyoto (WKY) and Sprague-Dawley rats. When estradiol treatment was given for 2 weeks, both SHR and DOCA-treated rats normalized their faulty hippocampal parameters, without evidences of effects in WKY or Sprague-Dawley rats. Thus, estradiol treatment of hypertensive rats positively modulated neurogenesis in the dentate gryus of the hippocampus, according to bromodeoxyuridine incorporation and doublecortin immunocytochemistry, decreased reactive astrocyte density, increased BDNF mRNA and protein expression in the dentate gyrus and increased neuronal number in the hilar region of the dentate gyrus We also investigated the potential role of local estrogen biosynthesis in SHR and WKY, by measuring the expression of aromatase, an enzyme involved in estrogen biosynthesis and neuroprotection. Real time PCR demonstrated increased basal aromatase mRNA expression in the brain of SHR, which was further increased after estradiol treatment. Increased immunoreactive aromatase expression was found in cell processes of the hilar region of the dentate gyrus of SHR respect of WKY. Estradiol treatment further increased the length of immunoreactive fibers in SHR but not in WKY. In conclusion, estradiol is neuroprotective to the hippocampus of hypertensive rat strains. A combination of exogenously administered estrogens plus those locally synthesized by estradiol-stimulated aromatase may better alleviate hypertensive encephalopathy. Supported by CONICET PIP 00542, PICT 0073, Santaló Project, Ubacyt MO16 and M614.