Neuromodulação da memória pelo eixo Angiotensina - (1-7)/ MAS

• Ano de defesa: 2013
• Autor(a) principal: Thiago Luiz do Nascimento Lazaroni
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; UFMG
• Palavras-chave em Português: Óxido nítrico; Eixo Angiotensina-(1-7)/Mas; Memória de reconhecimento de objetos; Memória de medo condicionado; Extinção de memórias; Sistema renina-angiotensina cerebral; Memória Fisiologia; Sistema renina-angiotensina Fisiologia; Oxído nítrico; Reconhecimento visual de modelos; Fisiologia
• Link de acesso: http://hdl.handle.net/1843/BUBD-9DFHUT

It is well known that the peptide Angiotensin-(1-7) [Ang-(1-7)] and its receptor Mas modulate cardiovascular function and more recently it has been shown that this axis also modulate cognition. Our laboratory previously showed that mice with genetic deletion of Mas receptor (MasKo) exhibit deficits in object recognition memory, which was reversed by the administration of losartan, an antagonist of Angiotensin II receptors AT1. In the present study, we investigated the molecular mechanisms responsible for object recognition memory deficits of MasKo, as well as the effect of losartan. Taken together, our results suggest that the memory deficit observed in MasKo mice is due to a down-regulation of the hippocampal nitrergic system. In addition, (1) considering that cardiovascular changes occur parallel to behavioral expression occurred during fear conditioning memory and (2) the MasKo mice are considered an animal model of hypertension, we also evaluated the modulation of Ang-(1-7)/Mas axis on consolidation, recall and extinction of fear memories. Our results showed that the knockout of Mas, depending of the mices background impaired the fear memory formation and extinction, which may be a consequence of an increased general fear and/or anxiety. Furthermore, we verified that the fear memory extinction deficit, as well as the increased anxiety levels was recovered by losartan. As a general conclusion we may suggest that the integrity of the Ang-(1-7)/Mas axis is essential for the maintenance of the nitrergic system which in turn is a important modulator of object memory. Furthermore, fear memories and cardiovascular functions may share at least one signaling pathway, the Ang-(1-7)/Mas axis.