Activation of ERα and/or ERβ ameliorates cognitive impairment and apoptosis in streptozotocin-induced diabetic mice

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 ER alpha and ER beta on the memory impairment and apoptosis in streptozotocin-induced diabetic mice. We found that ER alpha and/or ER beta 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 ER alpha and ER beta expression and subsequent PI3K/Akt, CREB and BDNF activation in the hippocampus of diabetic mice. Our data indicate that ER alpha and ER beta 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.