Substratos neurais envolvidos nos efeitos mnemônicos dos hormônios femininos

• Ano de defesa: 2010
• Autor(a) principal: Cristina dos Santos Fonseca
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; UFMG
• Palavras-chave em Português: Fisiologia e Farmacologia; Hormônios Efeito fisiológico; Fisiologia; Estradiol
• Link de acesso: http://hdl.handle.net/1843/BUOS-8DNH3N

Aging has a drastic effect on women due to menopause that occurs around the age of fifty and causes a significant reduction of ovarian steroids. Menopause is associated with memory loss and studies demonstrate that estrogen therapy can protect against this decrease in cognition. In an attempt to enlighten the effects of estrogens in cognition, this study evaluates the effect of reduced circulating 17- estradiol, through the removal of the ovary, in object recognition memory, andactivation of brain areas such as the hippocampus, amygdala and perirhinal cortex of the brain. Moreover, the effect of hormonal replacement was evaluated, after long period of deprivation, on memory and activation of the same neuronal substrates. Were used two month old female mice subjected to fake surgery (sham) or ovariectomy surgery (OVX). The novel recognition task was used to evaluate thecognition performance of mice one, six and twelve after the surgical procedure. To evaluate the effect of hormonal replacement after twelve weeks of surgery, the animals were divided into two groups: one that received subcutaneous capsules with oil, and other that received capsules containing 0.18 mg of 17-estradiol. After five weeks, the animals were subjected to the novel object recognition task. To assessneuronal activation in response to learning due to the task, was used c-Fos expression in the hippocampus, perirhinal cortex and amygdala. In the first protocol, the animals were divided in two groups: sham and OVX. Twelve weeks after the surgery, each group was sub-divided in to two groups: (1) box, mice that explored an empty box, named context and (2) animals that explored two equal objects, inside the same context. One hour and a half after, the animals were transcardially perfused and the brains were processed to perform a immunohistochemical procedure and determine the expression of c-Fos. In the second protocol, all the animals were ovariectomized and after twelve weeks split in to two groups: (1) animals that received subcutaneous capsules with oil, and (2) animals that received capsules containing 0.18 mg of 17-estradiol. After five weeks, the two groups were subdivided as described at the first protocol. Results show that OVX animals display memory loss after twelve weeks of hormonal deprivation and that hormonal replacement with 17-estradiol is able to partially revert this deficit. No significantdifferences were observed in the expression of c-Fos in the hippocampus, perirhinal cortex, basolateral and lateral amygdala for groups sham and OVX. However, a positive correlation was observed between exploration time of the objects and the expression of c-Fos in all above referred regions just for sham group. Moreover, there was a grater expression of c-Fos in the central nucleus of the amygdala for OVX animals exposed to the empty box compared to the sham group exposed to the same context. The hormonal replacement increased the expression of c-Fos in all the analyzed neural substrates and was able to induce an increase of c-Fos expression in the perirhinal cortex and central nucleus of the amygdala for animals that explored the box with objects. Altogether, the results suggest that estrogens are capable ofmodifying the activation of declarative memory relevant neural substrates, as the perirhinal cortex, and also important areas for neurovegetative answers, as the central nucleus of the amygdala. Therefore, part of the cognitive benefits and deficits related to the fluctuations of the estrogens levels can be explained by its ability to modify the activation of neural substrates required for consolidation and modulation of declarative memories.