| 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 |
Related Documents
:
|
3359304 - The presence of tyramine and related monoamines in the nerve cord and some other tissue... 20580984 - Tryptophan hydroxylase gene 1 (tph1) variants associated with cerebrospinal fluid 5-hyd... 19582224 - Precambrian lunar volcanic protolife. 3509064 - Effects of debrisoquin and haloperidol on plasma homovanillic acid concentration in sch... 7673304 - A study to determine the efficacy of treatments for hydrofluoric acid burns. 14535954 - Selective gamma-hydroxybutyric acid receptor ligands increase extracellular glutamate i... |
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: 2010-12-03 |
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 |
Affiliation:
|
Department of Molecular Biology and Center for Mass Spectrometry, The Scripps Research Institute, La Jolla, California 92037, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| 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 | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Mutations in the nervous system--specific HSN2 exon of WNK1 cause hereditary sensory neuropathy type...
Next Document: Variations in the G6PC2/ABCB11 genomic region are associated with fasting glucose levels.