Protective effects and the mechanisms of donepezil and galantamine on neuronal injury induced by glucose deprivation/reoxygenation
10.16438/j.0513-4870.2017-0485
- VernacularTitle:多奈哌齐和加兰他敏对氧糖剥夺/复氧导致的神经元损伤的保护作用及机制
- Author:
Dong-mei LIU
1
;
Man ZHANG
1
;
Xiao-mei JIANG
1
;
Hui LEI
1
;
Jiang LI
1
;
Xiao-liang WANG
1
Author Information
1. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
donepezil;
galantamine;
neuron apoptosis;
astrocyte;
neurotrophy
- From:
Acta Pharmaceutica Sinica
2017;52(6):928-935
- CountryChina
- Language:Chinese
-
Abstract:
Studies have shown that acetylcholinesterase inhibitors donepezil and galantamine have effects of reducing neuronal damage caused by glucose deprivation and reducing the cerebral infarction volume of cerebral ischemic animals, but their effects may not be entirely dependent on its inhibition of cholinesterase activity. In order to study the effects of donepezil and galantamine on neuronal injury of cerebral ischemia, the rat neuron-astrocyte co-culture model was successfully established in this study. In this model, we studied the effects of donepezil and galantamine on neuron apoptosis induced by oxygen-glucose deprivation/reoxygenation (OGD/R) and investigated the mechanism. The results showed that donepezil and galantamine significantly reduced the neuron apoptosis, and promoted the synthesis and secretion of BDNF and NGF in astrocytes in the co-culture system. Donepezil and galantamine activated the PI3K/Akt pathway and ERK pathway, and promoted the phosphorylation of the nuclear transcription factor CREB. These results suggest that donepezil and galantamine exhibit protective effects on neuronal damage induced by OGD/R. The mechanism may be related to activation of PI3K/Akt pathway and ERK pathway in astrocytes and promote phosphorylation of CREB, which lead to the synthesis and secretion of BDNF and NGF from astrocytes.
