Document Detail

Imaging brain signal transduction and metabolism via arachidonic and docosahexaenoic acid in animals and humans.
MedLine Citation:
PMID:  22178644     Owner:  NLM     Status:  MEDLINE    
The polyunsaturated fatty acids (PUFAs), arachidonic acid (AA, 20:4n-6) and docosahexaenoic acid (DHA, 22:6n-3), important second messengers in brain, are released from membrane phospholipid following receptor-mediated activation of specific phospholipase A(2) (PLA(2)) enzymes. We developed an in vivo method in rodents using quantitative autoradiography to image PUFA incorporation into brain from plasma, and showed that their incorporation rates equal their rates of metabolic consumption by brain. Thus, quantitative imaging of unesterified plasma AA or DHA incorporation into brain can be used as a biomarker of brain PUFA metabolism and neurotransmission. We have employed our method to image and quantify effects of mood stabilizers on brain AA/DHA incorporation during neurotransmission by muscarinic M(1,3,5), serotonergic 5-HT(2A/2C), dopaminergic D(2)-like (D(2), D(3), D(4)) or glutamatergic N-methyl-d-aspartic acid (NMDA) receptors, and effects of inhibition of acetylcholinesterase, of selective serotonin and dopamine reuptake transporter inhibitors, of neuroinflammation (HIV-1 and lipopolysaccharide) and excitotoxicity, and in genetically modified rodents. The method has been extended for the use with positron emission tomography (PET), and can be employed to determine how human brain AA/DHA signaling and consumption are influenced by diet, aging, disease and genetics.
Mireille Basselin; Epolia Ramadan; Stanley I Rapoport
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural; Review     Date:  2011-12-09
Journal Detail:
Title:  Brain research bulletin     Volume:  87     ISSN:  1873-2747     ISO Abbreviation:  Brain Res. Bull.     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-02-07     Completed Date:  2012-08-01     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  7605818     Medline TA:  Brain Res Bull     Country:  United States    
Other Details:
Languages:  eng     Pagination:  154-71     Citation Subset:  IM    
Copyright Information:
Published by Elsevier Inc.
Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
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MeSH Terms
Antidepressive Agents / therapeutic use
Arachidonic Acid / metabolism*
Brain / drug effects,  metabolism*,  radionuclide imaging
Brain Mapping*
Docosahexaenoic Acids / metabolism*
Models, Biological
Phospholipases A2 / metabolism
Signal Transduction / physiology*
Grant Support
Z01 AG000134-24/AG/NIA NIH HHS; Z01 AG000134-25/AG/NIA NIH HHS; Z01 AG000150-01/AG/NIA NIH HHS; Z01 AG000150-02/AG/NIA NIH HHS; ZIA AG000134-26/AG/NIA NIH HHS; ZIA AG000134-27/AG/NIA NIH HHS; ZIA AG000134-28/AG/NIA NIH HHS; ZIA AG000148-09/AG/NIA NIH HHS; ZIA AG000148-10/AG/NIA NIH HHS; ZIA AG000148-11/AG/NIA NIH HHS
Reg. No./Substance:
0/Antidepressive Agents; 25167-62-8/Docosahexaenoic Acids; 506-32-1/Arachidonic Acid; EC A2

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

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