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 ERβ on the memory impairment and apoptosis in streptozotocin-induced diabetic mice. We found that ERα and/or ERβ activation using their agonists (0.5 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 ERβ expression and subsequent PI3K/Akt, CREB and BDNF activation in the hippocampus of diabetic mice. Our data indicate that ERα and ERβ 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.
Keywords: Apoptosis; Cognition; Estrogen receptor α; Estrogen receptor β; Type 1 diabetes.
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