Document Detail


Toxicity of 6-hydroxydopamine and dopamine for dopaminergic neurons in culture.
MedLine Citation:
PMID:  1977925     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Toxicity of 6-hydroxydopamine (6-OHDA) and dopamine were studied in cultures of dissociated fetal rat mesencephalic cells. To assess survival and function of dopaminergic cells we quantified the number of tyrosine hydroxylase-positive cells and measured dopamine uptake. Non-dopaminergic cells were monitored by counting the number of cells visible with phase-contrast microscopy and measuring GABA uptake. 6-OHDA, in contrast to MPP+, which selectively destroyed dopaminergic neurons, was found to be a non-selective neurotoxin in this culture system. Between 10 and 100 microM, dopaminergic and non-dopaminergic cells were destroyed. At concentrations higher than 100 microM, i.e., concentrations frequently used to lesion catecholaminergic neurons in vivo, 6-OHDA resulted in structural fixation and loss of viability of dopaminergic and non-dopaminergic cells. Dopamine produced the same actions at slightly higher concentrations. One hundred to 300 microM was toxic for all cell types, and concentrations above 300 microM resulted in fixation. The findings suggest that 6-OHDA cannot be considered a selective toxin for catecholaminergic neurons in vitro. The demonstrated toxicity of dopamine tends to support speculations that processes related to dopamine metabolism may play a role in the pathogenesis of Parkinson's disease.
Authors:
P P Michel; F Hefti
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of neuroscience research     Volume:  26     ISSN:  0360-4012     ISO Abbreviation:  J. Neurosci. Res.     Publication Date:  1990 Aug 
Date Detail:
Created Date:  1990-12-05     Completed Date:  1990-12-05     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7600111     Medline TA:  J Neurosci Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  428-35     Citation Subset:  IM    
Affiliation:
Department of Neurology, University of Miami.
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MeSH Terms
Descriptor/Qualifier:
1-Methyl-4-phenylpyridinium / toxicity
Animals
Cells, Cultured
Dopamine / metabolism,  physiology,  toxicity*
Female
Fetus / physiology
Hydroxydopamines / toxicity*
Immunochemistry
Mesencephalon / cytology
Neurons / drug effects*
Oxidation-Reduction
Oxidopamine
Pregnancy
Rats
Rats, Inbred Strains
Trypan Blue / diagnostic use
Tyrosine 3-Monooxygenase / chemistry,  metabolism
gamma-Aminobutyric Acid / metabolism
Chemical
Reg. No./Substance:
0/Hydroxydopamines; 1199-18-4/Oxidopamine; 48134-75-4/1-Methyl-4-phenylpyridinium; 56-12-2/gamma-Aminobutyric Acid; 72-57-1/Trypan Blue; EC 1.14.16.2/Tyrosine 3-Monooxygenase

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


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