Document Detail


Human neuromelanin: an endogenous microglial activator for dopaminergic neuron death.
MedLine Citation:
PMID:  23276965     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Substantial evidence indicates that neuroinflammation caused by microglial activation in substantia nigra is critical in the pathogenesis of dopaminergic neurodegeneration in Parkinson's disease (PD). Increasing data demonstrates that environmental factors such as rotenone, paraquat play pivotal roles in dopaminergic neuron death. Here, potential role and mechanism of neuromelanin (NM), a major endogenous component in dopaminergic neurons of substantia nigra, on microglial activation and associated dopaminergic neurotoxicity were investigated. Using multiple primary mesencephalic cultures, we found that HNM caused dopaminergic neurodegeneration characterized by the decreased dopamine uptake and reduced numbers and shorted dendrites. HNM was selectively toxic to dopaminergic neurons since the other types of neurons determined by either gamma-aminobutyric acid uptake and total neuronal numbers showed smaller decrease. HNM produced modest dopaminergic neurotoxicity in neuron-enriched cultures; in contrast, much greater neurotoxicity was observed in the presence of microglia. HNM morphologically activated microglia and produced proinflammatory and neurotoxic factors. Thus, HNM can be a potent endogenous activator of microglial reactivation, mediating PD progression. Hence, inhibition of microglial reactivation can be a useful strategy for PD therapy.
Authors:
Wei Zhang; Luigi Zecca; Belinda Wilson; Hong-Wei Ren; Yong-Jun Wang; Xiao-Min Wang; Jau-Shyong Hong
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural     Date:  2013-01-01
Journal Detail:
Title:  Frontiers in bioscience (Elite edition)     Volume:  5     ISSN:  1945-0508     ISO Abbreviation:  Front Biosci (Elite Ed)     Publication Date:  2013  
Date Detail:
Created Date:  2013-01-01     Completed Date:  2013-06-05     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  101485240     Medline TA:  Front Biosci (Elite Ed)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1-11     Citation Subset:  IM    
Affiliation:
Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, PR China. ttyyzw@yahoo.com.cn
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Animals
Cell Death / physiology*
Cells, Cultured
Dendrites / drug effects,  physiology
Dopamine / metabolism
Dopaminergic Neurons / drug effects,  metabolism,  physiology*
Female
Humans
Immunohistochemistry
Melanins / metabolism*,  pharmacology
Microglia / physiology*
Nitric Oxide / metabolism
Parkinson Disease / metabolism,  physiopathology*
Pregnancy
Rats
Substantia Nigra / metabolism*
Tumor Necrosis Factor-alpha / metabolism
Grant Support
ID/Acronym/Agency:
ZIA ES090082-16/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Melanins; 0/Tumor Necrosis Factor-alpha; 0/neuromelanin; 10102-43-9/Nitric Oxide
Comments/Corrections

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