Efectos de esteroides en la patología del sistema nervioso”

DE NICOLA A.F.

Buenos Auires

Congreso; 14 Congreso Internacional de Medicina Interna del Hospital de Clinicas, Buenos Aires.; 2012

Hospital de Clinicas, UBA

Traditionally, estrogens have been considered prototype reproductive hormones, although their crucial protective effects for brain diseases are also recognized. Estrogen protective effects reach aging and age-associated diseases, including essential hypertension. Within the brain, the hippocampal formation is highly sensitive to the effects of hypertension, as exemplified in a genetic model of hypertension, the spontaneously hypertensive rat (SHR). SHR present decreased neurogenesis in the dentate gyrus, astrogliosis, low expression of brain derived neurotrophic factor (BDNF), decreased number of neurons in the hilar region and increased basal levels of the estrogen-synthesizing enzyme aromatase in the dentate gyrus, with respect to the Wistar Kyoto (WKY) normotensive strain. At the hypothalamic level, SHR also show increased expression of the hypertensinogenic peptide arginine vasopressin (AVP) and its V1b receptor. From the therapeutic point of view, it is highly rewarding that estradiol treatment of SHR decreases blood pressure and prevents or attenuates brain abnormalities of hypertension. Therefore, hypertension seems a suitable model to study estrogen neuroprotection. When estradiol treatment is given for 2 weeks, SHR normalize their faulty brain parameters, presenting increase neurogenesis in the dentate gryus of the hippocampus, according to bromodeoxyuridine incorporation and doublecortin immunocytochemistry, decrease reactive astrogliosis, increase BDNF mRNA and protein expression in the dentate gyrus, increase neuronal number in the hilar region of the dentate gyrus and further increase aromatase expression. The presence of estradiol receptors in hippocampus and hypothalamus suggest the possibility of direct effects of estradiol on brain cells.  Estradiol  neuroprotection in hypertensive rats should encourage trials using non-feminizing estrogens for age-associated diseases.