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褪黑素对 6-OHDA 损伤大鼠运动和记忆障碍的有益作用。

Beneficial Effect of Melatonin on Motor and Memory Disturbances in 6-OHDA-Lesioned Rats.

机构信息

Weston Visiting Professor of Weizmann Institute of Science, 234 Herzl Str, 76100, Rehovot, Israel.

Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. G, Bonchev Str., bl. 23, Sofia, 1113, Bulgaria.

出版信息

J Mol Neurosci. 2021 Apr;71(4):702-712. doi: 10.1007/s12031-020-01760-z. Epub 2021 Jan 5.

DOI:10.1007/s12031-020-01760-z
PMID:33403591
Abstract

Previous evidence has shown a link between neurodegenerative diseases, including Parkinson's disease (PD), and melatonin. The data in the literature about the impact of the hormone under different experimental PD conditions are quite controversial, and its effect on memory impairment in the disease is very poorly explored. The current research was aimed at investigating the role of melatonin pretreatment on memory and motor behavior in healthy rats and those with the partial 6-hydroxydopamine (6-OHDA) model of PD. All rodents were pretreated with melatonin (20 mg/kg, intraperitoneally) for 5 days. At 24 h and 7 days after the first treatment for healthy rats, and at the second and third week post-lesion for those with PD, the animals were tested behaviorally (apomorphine-induced rotations, rotarod, and passive avoidance tests). The neurochemical levels of dopamine (DA), acetylcholine (ACh), noradrenaline (NA), and serotonin (Sero) in the brain were also determined. The results showed that in healthy animals, melatonin pretreatment had amnestic and motor-suppressive effects and did not change the levels of measured brain neurotransmitters. In animals with PD, melatonin pretreatment exerted a neuroprotective effect, manifested as a significantly decreased number of apomorphine-induced rotations, reduced number of falls in the rotarod test, and improved memory performance. The brain DA and ACh concentrations in the same animals were restored to the control levels, and those of NA and Sero did not change. Our results demonstrate a beneficial effect of melatonin on memory and motor disturbance in 6-OHDA-lesioned rats.

摘要

先前的证据表明,神经退行性疾病(包括帕金森病)与褪黑素之间存在关联。文献中关于激素在不同实验性帕金森病条件下的影响的数据存在很大争议,其对疾病中记忆障碍的影响也尚未得到充分探索。本研究旨在研究褪黑素预处理对健康大鼠和部分 6-羟多巴胺(6-OHDA)帕金森病模型大鼠的记忆和运动行为的作用。所有啮齿动物均用褪黑素(20mg/kg,腹腔内注射)预处理 5 天。在健康大鼠第一次治疗后 24 小时和 7 天,以及帕金森病大鼠损伤后第二和第三周,对动物进行行为测试(阿扑吗啡诱导旋转、转棒和被动回避测试)。还测定了大脑中多巴胺(DA)、乙酰胆碱(ACh)、去甲肾上腺素(NA)和 5-羟色胺(Sero)的神经化学水平。结果表明,在健康动物中,褪黑素预处理具有健忘和运动抑制作用,且不改变所测脑神经递质的水平。在帕金森病动物中,褪黑素预处理发挥神经保护作用,表现为阿扑吗啡诱导旋转次数明显减少,转棒试验跌倒次数减少,记忆性能提高。同一动物的脑 DA 和 ACh 浓度恢复到对照水平,而 NA 和 Sero 浓度没有变化。我们的研究结果表明,褪黑素对 6-OHDA 损伤大鼠的记忆和运动障碍具有有益作用。

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