Envolvimento do sistema endocanabinóide no efeito promnésico induzido pelo exercício físico

• Ano de defesa: 2014
• Autor(a) principal: Talita Helen Ferreira e Vieira
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; UFMG
• Palavras-chave em Português: Hipocampo; Hidrolase de amida de ácido graxo; Esteira; AM251; Memória; Receptor canabinóide; Exercícios físicos; Hipocampo/metabolimo; Esteira rolante; Antagonista seletivo do receptor CB17; Receptores de canabinóides
• Link de acesso: http://hdl.handle.net/1843/BUOS-9MKJ8G

It is well known that physical exercise has positive effects on cognitive functions and hippocampal plasticity. The underlying mechanisms, however, have remained to be further investigated. Here we tested the hypothesis that the memory-enhancement promoted by physical exercise relies on facilitation of the endocannabinoid system. We observed that the spatial memory (not working memory) tested in the object location paradigm did not persist in sedentary mice, but could be improved by 1 week of treadmill running. In addition, exercise up-regulated both CB1 receptor (but not CB2) and BDNF expression (but not NT3, NT4 and NGF) in the hippocampus. It also induced increase in cellular proliferation, astrogliogenesis and neurogenesis in the dentate gyrus. No alterations were observed regarding anxiety- and depression-like behavrious and locomotor activity. To verify if the changes observed required the CB1 activation, we treated the mice with the selective antagonist, AM251, before each period of physical activity. In line with our hypothesis, this drug prevented the exerciseinduced memory enhancement and BDNF expression. Furthermore, AM251 blocked the increase of the CB1 expression and prevented the cellular proliferation, astrogliogenesis and neurogenesis. To test if facilitating the endocannabinoid system signaling would mimic the alterations observed after exercise, we treated sedentary animals during 1 week with the anandamide-hydrolysis inhibitor, URB597 (FAAH inhibitor). Mice treated with this drug improved spatial memory and have increased levels of CB1 and BDNF expression in the hippocampus as well as increased cellular proliferation, astrogliogenesis and neurogenesis, showing that potentiating the endocannabinoid system equally benefits memory. In summary, our results showed that the favorable effects of exercise upon spatial memory, BDNF expression, gliogenesis and neurogenesis depend of CB1 receptor signaling, which can be mimic, in sedentary animals, by inhibition of anandamide hydrolysis. Thus, our results suggest that, at least in part, the promnesic effect of the exercise is dependent of CB1 receptor activation and is mediated by BDNF, possibly by increased hippocampal neurogenesis.