Document Detail

Moderate degeneration of nigral neurons after repeated but not after single intrastriatal injections of low doses of 6-hydroxydopamine in mice.
MedLine Citation:
PMID:  18035334     Owner:  NLM     Status:  MEDLINE    
Parkinson's disease (PD) is characterized by a bilateral progressive degeneration of nigrostriatal dopaminergic neurons. Among several toxin-induced animal models of PD, a single intrastriatal injection of 6-hydroxydopamine (6-OHDA) has been reported to provoke a retrograde degeneration of nigral dopaminergic neurons and may reflect an early stage of PD. However, the lack of a progressive neuronal loss in those acute models limits the suitability for the assessment of neuroprotective therapeutics. Therefore, we investigated if repeated microinjections of 6-OHDA into the striatum of mice may generate a subchronic model with progressive degeneration. In contrast to acute bilateral microinjections of 8 microg 6-OHDA, repeated daily intrastriatal applications for 5 d provoked a moderate, but significant loss of nigral neurons. However, a longer treatment over 7 d failed to cause a more marked degeneration than observed after 5 d. Motor performance was unaltered after single and repeated treatments, except of a slight cataleptic behavior and shortened stride-length performance in mice treated over 7 d. The present data show for the first time that daily intrastriatal injections of 6-OHDA over 5 d can enhance the nigrostriatal neurodegeneration in mice. However, the extent of the neuronal loss was moderate and the technical expense limits the utility as a subchronic model.
Franziska Richter; Melanie Hamann; Angelika Richter
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-10-12
Journal Detail:
Title:  Brain research     Volume:  1188     ISSN:  0006-8993     ISO Abbreviation:  Brain Res.     Publication Date:  2008 Jan 
Date Detail:
Created Date:  2007-12-24     Completed Date:  2008-06-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  148-56     Citation Subset:  IM    
Institute of Pharmacology and Toxicology, Department of Veterinary Medicine, Freie Universität Berlin, Koserstr. 20, Berlin, Germany.
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MeSH Terms
Cell Count
Disease Models, Animal
Disease Progression
Dopamine / metabolism
Dose-Response Relationship, Drug
Drug Administration Schedule
Mice, Inbred C57BL
Nerve Degeneration / chemically induced*,  pathology,  physiopathology
Neurons / drug effects*,  pathology
Neurotoxins / toxicity
Oxidopamine / toxicity*
Parkinsonian Disorders / chemically induced*,  pathology,  physiopathology
Sympatholytics / toxicity
Time Factors
Tyrosine 3-Monooxygenase / metabolism
Reg. No./Substance:
0/Neurotoxins; 0/Sympatholytics; 1199-18-4/Oxidopamine; EC 3-Monooxygenase

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