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Effect of deep brain stimulation on substantia nigra neurons in a rat model of Parkinson's disease.
Chin Med J (Engl). 2012 Nov; 125(22):4072-5.CM

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.

Authors+Show Affiliations

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23158145

Citation

Wu, Sheng-tian, et al. "Effect of Deep Brain Stimulation On Substantia Nigra Neurons in a Rat Model of Parkinson's Disease." Chinese Medical Journal, vol. 125, no. 22, 2012, pp. 4072-5.
Wu ST, Ma Y, Zhang K, et al. Effect of deep brain stimulation on substantia nigra neurons in a rat model of Parkinson's disease. Chin Med J (Engl). 2012;125(22):4072-5.
Wu, S. T., Ma, Y., Zhang, K., & Zhang, J. G. (2012). Effect of deep brain stimulation on substantia nigra neurons in a rat model of Parkinson's disease. Chinese Medical Journal, 125(22), 4072-5.
Wu ST, et al. Effect of Deep Brain Stimulation On Substantia Nigra Neurons in a Rat Model of Parkinson's Disease. Chin Med J (Engl). 2012;125(22):4072-5. PubMed PMID: 23158145.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of deep brain stimulation on substantia nigra neurons in a rat model of Parkinson's disease. AU - Wu,Sheng-tian, AU - Ma,Yu, AU - Zhang,Kai, AU - Zhang,Jian-guo, PY - 2012/11/20/entrez PY - 2012/11/20/pubmed PY - 2013/12/16/medline SP - 4072 EP - 5 JF - Chinese medical journal JO - Chin Med J (Engl) VL - 125 IS - 22 N2 - 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. SN - 2542-5641 UR - https://www.unboundmedicine.com/medline/citation/23158145/Effect_of_deep_brain_stimulation_on_substantia_nigra_neurons_in_a_rat_model_of_Parkinson's_disease_ L2 - https://Insights.ovid.com/pubmed?pmid=23158145 DB - PRIME DP - Unbound Medicine ER -