Document Detail


Metabolomic analysis of the cerebrospinal fluid reveals changes in phospholipase expression in the CNS of SIV-infected macaques.
MedLine Citation:
PMID:  18521184     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
HIV infiltrates the CNS soon after an individual has become infected with the virus, and can cause dementia and encephalitis in late-stage disease. Here, a global metabolomics approach was used to find and identify metabolites differentially regulated in the cerebrospinal fluid (CSF) of rhesus macaques with SIV-induced CNS disease, as we hypothesized that this might provide biomarkers of virus-induced CNS damage. The screening platform used a non-targeted, mass-based metabolomics approach beginning with capillary reverse phase chromatography and electrospray ionization with accurate mass determination, followed by novel, nonlinear data alignment and online database screening to identify metabolites. CSF was compared before and after viral infection. Significant changes in the metabolome specific to SIV-induced encephalitis were observed. Metabolites that were increased during infection-induced encephalitis included carnitine, acyl-carnitines, fatty acids, and phospholipid molecules. The elevation in free fatty acids and lysophospholipids correlated with increased expression of specific phospholipases in the brains of animals with encephalitis. One of these, a phospholipase A2 isoenzyme, is capable of releasing a number of the fatty acids identified. It was expressed in different areas of the brain in conjunction with glial activation, rather than linked to regions of SIV infection and inflammation, indicating widespread alterations in infected brains. The identification of specific metabolites as well as mechanisms of their increase illustrates the potential of mass-based metabolomics to address problems in CNS biochemistry and neurovirology, as well as neurodegenerative diseases.
Authors:
William R Wikoff; Gurudutt Pendyala; Gary Siuzdak; Howard S Fox
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  118     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-07-03     Completed Date:  2008-09-25     Revised Date:  2014-04-08    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2661-9     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Carnitine / analogs & derivatives,  cerebrospinal fluid
Central Nervous System / enzymology,  metabolism*,  virology
Fatty Acids / cerebrospinal fluid
Gene Expression Regulation, Enzymologic
Group IV Phospholipases A2 / genetics,  metabolism
Hippocampus / metabolism
In Situ Hybridization
Lysophosphatidylcholines / cerebrospinal fluid
Macaca mulatta
Phospholipases / genetics*,  metabolism
Phospholipases A1 / genetics,  metabolism
Simian Acquired Immunodeficiency Syndrome / cerebrospinal fluid*,  metabolism
Simian immunodeficiency virus*
Spectrometry, Mass, Electrospray Ionization
Up-Regulation / genetics
Grant Support
ID/Acronym/Agency:
MH062261/MH/NIMH NIH HHS; MH073490/MH/NIMH NIH HHS; R01 MH073490-01/MH/NIMH NIH HHS; R01 MH073490-02/MH/NIMH NIH HHS; R01 MH073490-03/MH/NIMH NIH HHS; R01 MH073490-04/MH/NIMH NIH HHS; R01 MH073490-05/MH/NIMH NIH HHS; R01 MH073490-06/MH/NIMH NIH HHS; R01 MH073490-07A1/MH/NIMH NIH HHS; R01 MH073490-08/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/Fatty Acids; 0/Lysophosphatidylcholines; 541-15-1/Carnitine; EC 3.1.-/Phospholipases; EC 3.1.1.32/Phospholipases A1; EC 3.1.1.4/Group IV Phospholipases A2
Comments/Corrections

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