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首页> 外文期刊>Brain research >Protective effect of donepezil against Abeta(1-40) neurotoxicity in rat septal neurons.
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Protective effect of donepezil against Abeta(1-40) neurotoxicity in rat septal neurons.

机译：多奈哌齐对大鼠中隔神经元Abeta（1-40）神经毒性的保护作用。

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Donepezil, a potent acetylcholinesterase (AChE) inhibitor used for the treatment of Alzheimer's disease (AD), is thought to have a neuroprotective effect in AD patients. Because a deficit in cholinergic neurotransmission is a major feature in AD, and amyloid-beta (Abeta) accumulation has been proposed as a possible causative phenomenon, we were interested to examine the effect of donepezil on Abeta(1-40) induced neurotoxicity in primary cultures of rat septal neurons. Using immunohistochemical staining, almost all the neurons were found to be positive for vesicular acetylcholine transporter (VAChT) in these septal cultures. Septal neuronal cells were cultured for 7 days and then 15 micromol/L of Abeta(1-40) was added to the cell medium for 48 h. The cultured septal neurons were highly susceptible to Abeta toxicity, as shown by morphological examination and lactate dehydrogenase (LDH) assay. Donepezil concentration-dependently reduced the LDH efflux induced by Abeta(1-40), and the effect was significantat 100 nmol/L and above. Donepezil decreased both the negative peak at around 215 nm in the circular dichroism (CD) spectrum and the fluorescence intensity of thioflavin T in the presence of Abeta(1-40). These results suggest that donepezil exerts a neuroprotective effect by reducing the amount of the toxic form of Abeta fibrils in septal neuron cultures. These findings support the idea that the clinical efficacy of donepezil in AD is due to not only activation of cholinergic transmission, but also attenuation of neuronal damage.
机译：多奈哌齐是一种有效的乙酰胆碱酯酶（AChE）抑制剂，用于治疗阿尔茨海默氏病（AD），据认为对AD患者具有神经保护作用。因为胆碱能神经传递的不足是AD的主要特征，并且已经提出淀粉样β（Abeta）积累是一种可能的病因，所以我们有兴趣研究多奈哌齐对Abeta（1-40）诱导的原发性神经毒性的影响间隔神经元的培养。使用免疫组织化学染色，发现这些间隔培养物中几乎所有神经元的囊泡乙酰胆碱转运蛋白（VAChT）均为阳性。间隔神经元细胞培养7天，然后将15 micromol / L Abeta（1-40）加入细胞培养基中48 h。如形态学检查和乳酸脱氢酶（LDH）分析所示，培养的间隔神经元对Abeta毒性高度敏感。多奈哌齐浓度依赖性地降低由Abeta（1-40）诱导的LDH外排，并且在100 nmol / L及以上时效果显着。多奈哌齐降低了圆二色性（CD）光谱中215 nm附近的负峰和存在Abeta（1-40）时硫黄素T的荧光强度。这些结果表明，多奈哌齐通过减少间隔神经元培养物中Abeta原纤维的毒性形式的数量而发挥神经保护作用。这些发现支持了多奈哌齐在AD中的临床疗效不仅归因于胆碱能传递的激活，还归因于神经元损伤的减弱。

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