RESUMO
Estrogen receptors (ERs) are thought to be associated with the onset and progression of neurodegenerative injuries and diseases, but the relationship and mechanisms underlying between ERs and cognition in type 2 diabetes remain elusive. In the current study, we investigated the effects of ERα and ERß on the cognition, neurogenesis and apoptosis in high-fat diet and streptozocin-induced diabetic mice. We found that ERα and/or ERß activation using their agonists (0.5â¯mg/kg E2, PPT or DPN) ameliorate memory impairment in the Morris water maze and Y-maze tests, increase hippocampal neurogenesis and prevent hippocampal apoptotic responses. Importantly, treatment with the pharmacologic ERs agonists caused significant increases in the membrane ERα and ERß expression and subsequent PI3K/Akt, CREB and BDNF activation in the hippocampus of type 2 diabetes mellitus mice. Our data indicate that ERα and ERß are involved in the cognitive impairment in type 2 diabetes, and that activated ERs, such as application of ERs agonists, could be a novel and promising strategy for the treatment of diabetic cognitive impairment.
Assuntos
Apoptose/fisiologia , Disfunção Cognitiva/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Neurogênese/fisiologia , Animais , Apoptose/efeitos dos fármacos , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/psicologia , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/psicologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/psicologia , Estradiol/farmacologia , Estradiol/uso terapêutico , Receptor alfa de Estrogênio/agonistas , Receptor beta de Estrogênio/agonistas , Feminino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Endogâmicos ICR , Neurogênese/efeitos dos fármacos , Distribuição AleatóriaRESUMO
Estrogen receptors (ERs) are thought to be associated with the onset and progression of neurodegenerative injuries and diseases, but the relationship and mechanisms underlying between ERs and cognition in type 1 diabetes remain elusive. In the current study, we investigated the effects of ERα and ERß on the memory impairment and apoptosis in streptozotocin-induced diabetic mice. We found that ERα and/or ERß activation using their agonists (0.5â¯mg/kg E2, PPT or DPN) ameliorate memory impairment in the Morris water maze (MWM) and Y-maze tests and suppress apoptosis as evidenced by decreased caspase-3 activity and increased ratio of Bcl-2/Bax. Importantly, treatment with the pharmacologic ERs agonists caused significant increases in the membrane ERα and ERß expression and subsequent PI3K/Akt, CREB and BDNF activation in the hippocampus of diabetic mice. Our data indicate that ERα and ERß are involved in the cognitive impairment of type 1 diabetes and that activation of ERs via administration of ERs agonists could be a novel and promising strategy for the treatment of diabetic cognitive impairment.