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低剂量鱼藤酮持续灌胃处理致中脑多巴胺能神经元损伤

黄梦阳 江红 胡琦 康慧聪 许峰 刘晓艳 张存泰 朱遂强

神经损伤与功能重建Issue(3):199-202,4.
神经损伤与功能重建Issue(3):199-202,4.DOI:10.3870/sjsscj.2014.03.008

低剂量鱼藤酮持续灌胃处理致中脑多巴胺能神经元损伤

Dopaminergic Neuron Damage induced by Constant Intragastric Administration of Low-dose Rotenone

黄梦阳 1江红 1胡琦 1康慧聪 2许峰 2刘晓艳 2张存泰 1朱遂强2

作者信息

  • 1. 华中科技大学同济医学院附属同济医院 综合科 武汉 430030
  • 2. 华中科技大学同济医学院附属同济医院 神经内科 武汉 430030
  • 折叠

摘要

Abstract

ObjectiveTo explore the mechanism of dopaminergic neuron damage induced by constant intragas-tric administration of low-dose rotenone. Methods: Fifty aged male mice were randomly divided into Parkinson disease (PD) model group and control group. The mice in PD model group were administrated 0.01 mL/g rotenone by gavage while the mice in control group were administrated 0.01 mL/g chloroform. Before treatment and 6 weeks, as well as 12 weeks after treatment, alpha-synuclein (α-Syn), Thioflavin S (ThS) and tyrosine hydroxylase (TH) were detected in neurons from gastrointestinal tract, thoracic spinal cord and midbrain of both the control and treated animals. Simultaneously, ultrastructural changes were observed by electron microscopy 12 weeks after treatment. Results: Six weeks after treatment, immunofluorescence demonstrated that α-Syn and ThS were increased in intestinal intramural plexus and thoracic spinal cord in the PD model group compared to the controls while the expression of α-Syn and number of TH positive neurons in midbrain did not show any significant changes( >0.05). However, 12 weeks after treatment, immunofluorescence showed that there was an increase inα-Syn and an significant decrease in TH positive neurons in the midbrain ( =0.011) in the model group compared with those in the controls. Moreover, electron microscopy showed a lot of abnormalities in the PD model group, such as the swollenness of cell membrane, mitochondria and endoplasmic reticulum, alterations of nuclei, and necrosis of neurons in the substantia nigra, in a sharp contrast to the normality in the .control group. Conclusion:Dopaminergic neuron damage was observed in mouse brain after constant intragastric administration of low-dose rotenone, probably mediated by the spread of synuclein aggregates formed in gastrointestinal plexues into brain by prion-like transmission.

关键词

帕金森病/鱼藤酮/α- 突触核蛋白/多巴胺能神经元

Key words

Parkinson's disease/rotenone/alpha-synuclein/dopaminergic neuron

分类

医药卫生

引用本文复制引用

黄梦阳,江红,胡琦,康慧聪,许峰,刘晓艳,张存泰,朱遂强..低剂量鱼藤酮持续灌胃处理致中脑多巴胺能神经元损伤[J].神经损伤与功能重建,2014,(3):199-202,4.

基金项目

国家自然科学基金青年基金 ()

神经损伤与功能重建

OACSTPCD

1001-117X

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