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Effect of deep brain stimulation on substantia nigra neurons in a rat model of Parkinson's disease

WU Sheng-tian MA Yu ZHANG Kai ZHANG Jian-guo

中华医学杂志(英文版)2012,Vol.125Issue(22):4072-4075,4.
中华医学杂志(英文版)2012,Vol.125Issue(22):4072-4075,4.DOI:10.3760/cma.j.issn.0366-6999.2012.22.029

Effect of deep brain stimulation on substantia nigra neurons in a rat model of Parkinson's disease

Effect of deep brain stimulation on substantia nigra neurons in a rat model of Parkinson's disease

WU Sheng-tian 1MA Yu 2ZHANG Kai 1ZHANG Jian-guo1

作者信息

  • 1. Department of Neurosurgery,Beijing Tiantan Hospital,Capital Medical University,Beijing 100050,China
  • 2. Beijing Neurosurgical Institute,Beijing 100050,China
  • 折叠

摘要

Abstract

Background Parkinson's disease(PD)is a common neurodegenerative disease,which occurs mainly in the elderly.Recent studies have demonstrated that apoptosis plays an important role in the occurrence and development of PD.Subthalamic nucleus deep brain stimulation(STN-DBS)has been recognized as an effective treatment for PD.Recent clinical observations have shown that STN-DBS was able to delay early PD progression,and experiments in animal models have also demonstrated a protective effect of STN-DBS on neurons.However,the correlation between the neuron-protective effect of STN-DBS and the progression of substantia nigra pars compacta(SNc)neuronal apoptosis is still unknown.The aim of this study was to investigate the protective effect and potential mechanism of STN-DBS on SNc neurons in PD rats.Methods After the establishment of a PD rat model by unilateral/2-point injection of 6-hydroxydopamine in the medial forebrain bundle of the brain,DBS by implanting electrodes in the STN was administered.Behavioral changes were observed,and morphological changes of SNc neurons were analyzed by Nissl staining and DNA in situ end-labeling.Through extracellular recording of single neuron discharges and microelectrophoresis,the causes of and changes in SNc excitability during STN-DBS were analyzed,and the protective effect and potential mechanism of action of STN-DBS on SNc neurons in PD rats was investigated.Results SNc neuron apoptosis was significantly decreased(P<0.05)in the stimulation group,compared with the sham stimulation PD group.Spontaneous discharges of SNc neurons were observed in normal rats and PD model rats,and the mean frequency of spontaneous discharges of SNc neurons in normal rats((40.65±11.08)Hz)was higher than that of residual SNc neurons in PD rats((36.71±9.23)Hz).Electrical stimulation of the STN in rats was associated with elevated excitation in unilateral SNc neurons.However,administering the gamma-aminobutyric acid receptor blocker,bicuculline significantly reduced SNc neuron excitation,but the change in SNc neuron excitation was not present when MK801,a glutamate receptor blocker,was administered.Conclusions High-frequency stimulation of the STN has a protective effect on SNc neurons in PD rats.The possible molecular mechanism may be related to changes in the distribution and metabolism of neurotransmitters in the SNc region.

关键词

Parkinson's disease/apoptosis/deep brain stimulation/excitatory neurotransmitter

Key words

Parkinson's disease/apoptosis/deep brain stimulation/excitatory neurotransmitter

引用本文复制引用

WU Sheng-tian,MA Yu,ZHANG Kai,ZHANG Jian-guo..Effect of deep brain stimulation on substantia nigra neurons in a rat model of Parkinson's disease[J].中华医学杂志(英文版),2012,125(22):4072-4075,4.

基金项目

This work was supported by grants from the National Natural Science Foundation of China(No.81070901,No.81141013)and Beijing Outstanding Talents Project(No.2011D003034000019). (No.81070901,No.81141013)

中华医学杂志(英文版)

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