ERα and/or ERβ activation ameliorates cognitive impairment, neurogenesis and apoptosis in type 2 diabetes mellitus mice
| Autor: | Su-Su Tang, Hao Hong, Yi Ren, Qing-Hua Hu, Jing-Ran Cao, Xiao-Qian Ren, Hui Ji |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Neurogenesis Estrogen receptor Morris water navigation task Apoptosis Type 2 diabetes CREB Diabetes Mellitus Experimental Mice Random Allocation 03 medical and health sciences 0302 clinical medicine Developmental Neuroscience Internal medicine medicine Animals Estrogen Receptor beta Cognitive Dysfunction Maze Learning Protein kinase B PI3K/AKT/mTOR pathway Mice Inbred ICR Estradiol biology business.industry Estrogen Receptor alpha Type 2 Diabetes Mellitus medicine.disease 030104 developmental biology Endocrinology Diabetes Mellitus Type 2 Neurology biology.protein Female business 030217 neurology & neurosurgery |
| Zdroj: | Experimental Neurology. 311:33-43 |
| ISSN: | 0014-4886 |
| DOI: | 10.1016/j.expneurol.2018.09.002 |
| Popis: | 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 ERβ on the cognition, neurogenesis and apoptosis in high-fat diet and streptozocin-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 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 ERβ expression and subsequent PI3K/Akt, CREB and BDNF activation in the hippocampus of type 2 diabetes mellitus mice. Our data indicate that ERα and ERβ 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. |
| Databáze: | OpenAIRE |
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