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GM1神经节苷脂治疗可促进MPTP诱导的帕金森病小鼠模型纹状体多巴胺浓度的恢复。

GM1 ganglioside treatment promotes recovery of striatal dopamine concentrations in the mouse model of MPTP-induced parkinsonism.

作者信息

Schneider J S, Yuwiler A

机构信息

Department of Neurology, Hahnemann University School of Medicine, Philadelphia, Pennsylvania 19102.

出版信息

Exp Neurol. 1989 Aug;105(2):177-83. doi: 10.1016/0014-4886(89)90117-9.

Abstract

GM1 ganglioside (GM1) has in the past been reported to promote regenerative sprouting and functional recovery in both central and peripheral nervous systems. The present experiments were performed in order to investigate whether GM1 might have any therapeutic effect on young mice who had been exposed to the Parkinson-producing neurotoxin MPTP. GM1 caused moderate to dramatic increases in striatal dopamine levels, depending upon duration of exposure to GM1, in animals previously exposed to MPTP. Furthermore, the effects of GM1 on enhancing striatal dopamine levels were apparent when GM1 administration was delayed until 3 days after the last MPTP injection was given and these effects were not reversed when GM1 was withdrawn. Tyrosine hydroxylase (TH) immunohistochemistry of the striatum demonstrated increased numbers of TH-positive fibers and TH-positive terminal fields in GM1-treated animals as compared to animals that received only MPTP. TH immunohistochemistry of the substantia nigra revealed little or no loss of parts compacta neurons in the MPTP-treated mice. On the basis of these observations, GM1 appears to increase the dopamine content of the striatum by promoting or stimulating regenerative sprouting of dopaminergic terminals and perhaps collateral sprouting from remaining intact fibers in the MPTP model of Parkinsonism in the young mouse. We suggest that GM1 ganglioside may hold some promise as a potential adjunct in the treatment of Parkinson's Disease.

摘要

过去有报道称,GM1神经节苷脂(GM1)可促进中枢和外周神经系统的再生发芽及功能恢复。进行本实验是为了研究GM1对暴露于帕金森病致病神经毒素MPTP的幼鼠是否具有治疗作用。在先前暴露于MPTP的动物中,根据GM1的暴露持续时间,GM1可使纹状体多巴胺水平适度至显著升高。此外,当GM1给药延迟至最后一次MPTP注射后3天时,GM1对提高纹状体多巴胺水平的作用依然明显,且停用GM1后这些作用并未逆转。与仅接受MPTP处理的动物相比,GM1处理动物纹状体的酪氨酸羟化酶(TH)免疫组化显示TH阳性纤维和TH阳性终末场数量增加。黑质的TH免疫组化显示,MPTP处理小鼠的致密部神经元几乎没有损失或仅有少量损失。基于这些观察结果,在幼鼠帕金森病MPTP模型中,GM1似乎通过促进或刺激多巴胺能终末的再生发芽以及可能来自剩余完整纤维的侧支发芽来增加纹状体的多巴胺含量。我们认为,GM1神经节苷脂作为帕金森病治疗的潜在辅助药物可能具有一定前景。

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