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High-frequency stimulation of the globus pallidus interna nucleus modulates GFRα1 gene expression in the basal ganglia.
MedLine Citation:
PMID:  24291478     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Deep brain stimulation (DBS) is an established therapy for movement disorders such as Parkinson's disease (PD). Although the efficacy of DBS is clear, its precise molecular mechanism remains unknown. The glial cell line derived factor (GDNF) family of ligands has been shown to confer neuroprotective effects on dopaminergic neurons, and putaminal infusion of GDNF have been investigated in PD patients with promising results. Despite the potential therapeutic role of GDNF in alleviating motor symptoms, there is no data on the effects of electrical stimulation on GDNF-family receptor (GFR) expression in the basal ganglia structures. Here, we report the effects of electrical stimulation on GFRα1 isoforms, particularly GFRα1a and GFRα1b. Wistar rats underwent 2hours of high frequency stimulation (HFS) at the globus pallidus interna nucleus. A control group was subjected to a similar procedure but without stimulation. The HFS group, sacrificed 24hours after treatment, had a threefold decrease in mRNA expression level of GFRα1b (p=0.037), but the expression level reverted to normal 72hours after stimulation. Our preliminary data reveal the acute effects of HFS on splice isoforms of GFRα1, and suggest that HFS may modulate the splice isoforms of GFRα1a and GFRα1b to varying degrees. Going forward, elucidating the interactions between HFS and GFR may shed new insights into the complexity of GDNF signaling in the nervous system and lead to better design of clinical trials using these signaling pathways to halt disease progression in PD and other neurodegenerative diseases.
Authors:
Duncun Xun Kiat Ho; Yong Chee Tan; Jiayi Tan; Heng Phon Too; Wai Hoe Ng
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-8-15
Journal Detail:
Title:  Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia     Volume:  -     ISSN:  1532-2653     ISO Abbreviation:  J Clin Neurosci     Publication Date:  2013 Aug 
Date Detail:
Created Date:  2013-12-2     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9433352     Medline TA:  J Clin Neurosci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2013 Elsevier Ltd. All rights reserved.
Affiliation:
Department of Neurosurgery, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore. Electronic address: duncun_xk_ho@nni.com.sg.
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