Comparison of donepezil and memantine for protective effect against amyloid-beta(1–42) toxicity in rat septal neurons
Comparison of donepezil and memantine for protective effect against amyloid-beta(1–42) toxicity in rat septal neurons
复制标题
多奈哌齐和美金刚对大鼠间隔神经元淀粉样蛋白-β(1-42)毒性的保护作用比较
DOI：
10.1016/j.neulet.2005.08.036
复制
发表时间：
2005
影响因子：
2.5
通讯作者：
K. Sawada
中科院分区：
文献类型：
--
作者：
Manami Kimura;H. Komatsu;H. Ogura;K. Sawada
多奈哌齐（一种强效的乙酰胆碱酯酶（AChE）抑制剂）和美金刚（一种N-甲基-d-天冬氨酸（NMDA）受体拮抗剂）已被用于治疗阿尔茨海默病（AD），并且两者均被证明具有神经保护作用针对谷氨酸兴奋性毒性。然而，尚不清楚多奈哌齐和美金刚是否对胆碱能神经元中的淀粉样β肽（1-42）[Aβ（1-42）]毒性具有类似的神经保护作用。因此，在本研究中，我们比较了多奈哌齐和美金刚对培养的大鼠隔胆碱能神经元Aβ（1-42）毒性的神经保护作用，因为胆碱能神经传递缺陷是AD的主要特征，并且已知AD患者内侧隔胆碱能神经元退化。培养7 d后加入5μmol/L Aβ（1-42）培养48 h。乳酸脱氢酶（LDH）外排的测定表明隔神经元对Aβ毒性高度敏感，对NMDA毒性相对抵抗。多奈哌齐呈浓度依赖性地减少Aβ（1-42）诱导的LDH外排，1μmol/L及以上浓度时作用显著。NMDA受体拮抗剂美金刚和MK-801对Aβ（1-42）毒性无明显神经保护作用。结论：多奈哌齐对Aβ（1-42）毒性的神经保护作用不是通过干扰NMDA介导的兴奋性毒性过程来介导的，多奈哌齐可能比美金刚更有效地对抗Aβ（1-42）暴露引起的胆碱能神经元损伤。
Donepezil, a potent acetylcholinesterase (AChE) inhibitor and memantine, an N-methyl-d-aspartate (NMDA) receptor antagonist, have been used for the treatment of Alzheimer's disease (AD), and both of them have been shown to have neuroprotective action against glutamate excitotoxicity. However, it is not known whether donepezil and memantine similarly exert neuroprotective effects against amyloid-beta peptide(1–42) [Aβ(1–42)] toxicity in cholinergic neurons. Therefore, in the present study we compared the neuroprotective effects of donepezil and memantine against Aβ(1–42) toxicity in rat cultured septal cholinergic neurons, because deficit in cholinergic neurotransmission is a major feature in AD, and medial septal cholinergic neurons are known to degenerate in AD patients. Septal neuronal cells were cultured for 7 days and then 5μmol/L of Aβ(1–42) was added to the medium for 48h. Measurement of the efflux of lactate dehydrogenase (LDH) indicated that septal neuronal cells were highly susceptible to Aβ toxicity and relatively resistant to NMDA toxicity. Donepezil concentration-dependently reduced the LDH efflux induced by Aβ(1–42), and the effect was significant at 1μmol/L and above. NMDA receptor antagonists, memantine and MK-801, did not show a significant neuroprotective effect against Aβ(1–42) toxicity. It is concluded that the neuroprotective effect of donepezil against Aβ(1–42) toxicity is not mediated by interference with the NMDA-mediated excitotoxic process, and that donepezil may be more effective than memantine against cholinergic neuronal damage induced by Aβ(1–42) exposure.
影响因子：
56.9
作者：
COYLE, JT;PRICE, DL;DELONG, MR
通讯作者：
DELONG, MR