| Transgenic conversion of omega-6 into omega-3 fatty acids in a mouse model of Parkinson's disease. | |
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MedLine Citation:
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PMID: 21115966 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We have recently identified a neuroprotective role for omega-3 polyunsaturated fatty acids (n-3 PUFAs) in a toxin-induced mouse model of Parkinson's disease (PD). Combined with epidemiological data, these observations suggest that low n-3 PUFA intake is a modifiable environmental risk factor for PD. In order to strengthen these preclinical findings as prerequisite to clinical trials, we further investigated the neuroprotective role of n-3 PUFAs in Fat-1 mice, a transgenic model expressing an n-3 fatty acid desaturase converting n-6 PUFAs into n-3 PUFAs. Here, we report that the expression of the fat-1 transgene increased cortical n-3:n-6 PUFA ratio (+28%), but to a lesser extent than dietary supplementation (92%). Such a limited endogenous production of n-3 PUFAs in the Fat-1 mouse was insufficient to confer neuroprotection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity as assessed by dopamine levels, tyrosine hydroxylase (TH)-positive neurons and fibers, as well as nigral Nurr1 and dopamine transporter (DAT) mRNA expression. Nevertheless, higher cortical docosahexaenoic acid (DHA) concentrations were positively correlated with markers of nigral dopaminergic neurons such as the number of TH-positive cells, in addition to Nurr1 and DAT mRNA levels. These associations are consistent with the protective role of DHA in a mouse model of PD. Taken together, these data suggest that dietary intake of a preformed DHA supplement is more effective in reaching the brain and achieving neuroprotection in an animal model of PD. |
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Authors:
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Melanie Bousquet; Karl Gue; Vincent Emond; Pierre Julien; Jing X Kang; Francesca Cicchetti; Frederic Calon |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-11-29 |
Journal Detail:
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Title: Journal of lipid research Volume: 52 ISSN: 0022-2275 ISO Abbreviation: J. Lipid Res. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-01-17 Completed Date: 2011-05-05 Revised Date: 2012-02-01 |
Medline Journal Info:
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Nlm Unique ID: 0376606 Medline TA: J Lipid Res Country: United States |
Other Details:
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Languages: eng Pagination: 263-71 Citation Subset: IM |
Affiliation:
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Centre de Recherche du CHUL (CHUQ), Axe Neurosciences, Québec, QC, Canada. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Disease Models, Animal Docosahexaenoic Acids / metabolism Fatty Acids, Omega-3 / metabolism Mice Neuroprotective Agents / pharmacology Parkinson Disease, Secondary / chemically induced, metabolism* Transgenes |
| Grant Support | |
ID/Acronym/Agency:
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CAN-76833//Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
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0/Fatty Acids, Omega-3; 0/Neuroprotective Agents; 25167-62-8/Docosahexaenoic Acids |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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