Document Detail


Neuroprotective and anti-inflammatory properties of a coffee component in the MPTP model of Parkinson's disease.
MedLine Citation:
PMID:  23296837     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Consumption of coffee is associated with reduced risk of Parkinson's disease (PD), an effect that has largely been attributed to caffeine. However, coffee contains numerous components that may also be neuroprotective. One of these compounds is eicosanoyl-5-hydroxytryptamide (EHT), which ameliorates the phenotype of α-synuclein transgenic mice associated with decreased protein aggregation and phosphorylation, improved neuronal integrity and reduced neuroinflammation. Here, we sought to investigate if EHT has an effect in the MPTP model of PD. Mice fed a diet containing EHT for four weeks exhibited dose-dependent preservation of nigral dopaminergic neurons following MPTP challenge compared to animals given control feed. Reductions in striatal dopamine and tyrosine hydroxylase content were also less pronounced with EHT treatment. The neuroinflammatory response to MPTP was markedly attenuated, and indices of oxidative stress and JNK activation were significantly prevented with EHT. In cultured primary microglia and astrocytes, EHT had a direct anti-inflammatory effect demonstrated by repression of lipopolysaccharide-induced NFκB activation, iNOS induction, and nitric oxide production. EHT also exhibited a robust anti-oxidant activity in vitro. Additionally, in SH-SY5Y cells, MPP(+)-induced demethylation of phosphoprotein phosphatase 2A (PP2A), the master regulator of the cellular phosphoregulatory network, and cytotoxicity were ameliorated by EHT. These findings indicate that the neuroprotective effect of EHT against MPTP is through several mechanisms including its anti-inflammatory and antioxidant activities as well as its ability to modulate the methylation and hence activity of PP2A. Our data, therefore, reveal a strong beneficial effect of a novel component of coffee in multiple endpoints relevant to PD.
Authors:
Kang-Woo Lee; Joo-Young Im; Jong-Min Woo; Hilary Grosso; Yoon-Seong Kim; Ana Clara Cristovao; Patricia K Sonsalla; David S Schuster; Marla M Jalbut; Jose R Fernandez; Michael Voronkov; Eunsung Junn; Steven P Braithwaite; Jeffry B Stock; M Maral Mouradian
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics     Volume:  10     ISSN:  1878-7479     ISO Abbreviation:  Neurotherapeutics     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-29     Completed Date:  2013-07-29     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  101290381     Medline TA:  Neurotherapeutics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  143-53     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Inflammatory Agents / pharmacology*
Blotting, Western
Chromatography, High Pressure Liquid
Coffee / chemistry*
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry
MPTP Poisoning / metabolism,  prevention & control*
Male
Mice
Mice, Inbred C57BL
Neuroprotective Agents / pharmacology*
Plant Extracts / pharmacology*
Grant Support
ID/Acronym/Agency:
AT006868/AT/NCCAM NIH HHS; NS059869/NS/NINDS NIH HHS; NS070898/NS/NINDS NIH HHS; NS073994/NS/NINDS NIH HHS; R01 AT006868/AT/NCCAM NIH HHS; R01 NS062827/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents; 0/Coffee; 0/Neuroprotective Agents; 0/Plant Extracts
Comments/Corrections

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


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