Document Detail

Survival of midbrain dopaminergic cells after lesion or deep brain stimulation of the subthalamic nucleus in MPTP-treated monkeys.
MedLine Citation:
PMID:  17584773     Owner:  NLM     Status:  MEDLINE    
We have examined dopaminergic cell survival after alteration of the subthalamic nucleus (STN) in methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys. The STN was lesioned with kainic acid (B series) or underwent deep brain stimulation (DBS) at high frequency (C series). In another series, MPTP-treated and non-MPTP-treated monkeys had no STN alteration (intact animals; A series). Animals were treated with MPTP either after (B1, C1) or before (B2, C2) STN alteration. We also explored the long-term ( approximately 7 months) effect of DBS in non-MPTP-treated monkeys (D series). Brains were aldehyde-fixed and processed for routine Nissl staining and tyrosine hydroxylase immunocytochemistry. Our results showed that there were significantly more (20-24%) dopaminergic cells in the substantia nigra pars compacta (SNc) of the MPTP-treated monkeys that had STN alteration, either with kainic acid lesion or DBS, compared to the non-MPTP-treated monkeys (intact animals). We suggest that this saving or neuroprotection was due to a reduction in glutamate excitotoxicity, as a result of the loss or reduction of the STN input to the SNc. Our results also showed that SNc cell number in the B1 and C1 series were very similar to those in the B2 and C2 series. In the cases that had long-term DBS of the STN (D series), there was no adverse impact on SNc cell number. In summary, these results indicated that STN alteration offered neuroprotection to dopaminergic cells that would normally die as part of the disease process.
Bradley A Wallace; Keyoumars Ashkan; Claire E Heise; Kelly D Foote; Napoleon Torres; John Mitrofanis; Alim-Louis Benabid
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-06-20
Journal Detail:
Title:  Brain : a journal of neurology     Volume:  130     ISSN:  1460-2156     ISO Abbreviation:  Brain     Publication Date:  2007 Aug 
Date Detail:
Created Date:  2007-07-31     Completed Date:  2007-09-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372537     Medline TA:  Brain     Country:  England    
Other Details:
Languages:  eng     Pagination:  2129-45     Citation Subset:  AIM; IM    
Department of Clinical and INSERM U318 Preclinical Neurosciences, University Joseph Fourier, Grenoble, France.
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MeSH Terms
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / pharmacology*
Cell Survival / drug effects
Deep Brain Stimulation*
Dopamine / metabolism*
Kainic Acid
Macaca fascicularis
Neurons / drug effects
Neurotoxins / pharmacology
Severity of Illness Index
Substantia Nigra / drug effects*,  metabolism,  pathology
Subthalamic Nucleus / drug effects*,  pathology
Reg. No./Substance:
0/Neurotoxins; 28289-54-5/1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; 487-79-6/Kainic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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