Document Detail


Docosahexaenoic acid (DHA) incorporation into the brain from plasma, as an in vivo biomarker of brain DHA metabolism and neurotransmission.
MedLine Citation:
PMID:  21704722     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Docosahexaenoic acid (DHA) is critical for maintaining normal brain structure and function, and is considered neuroprotective. Its brain concentration depends on dietary DHA content and hepatic conversion from its dietary derived n-3 precursor, α-linolenic acid (α-LNA). We have developed an in vivo method in rats using quantitative autoradiography and intravenously injected radiolabeled DHA to image net incorporation into the brain of unesterified plasma DHA, and showed with this method that the incorporation rate of DHA equals the rate of brain metabolic DHA consumption. The method has been extended for use in humans with positron emission tomography (PET). Furthermore, imaging in unanesthetized rats using DHA incorporation as a biomarker in response to acute N-methyl-D-aspartate administration confirms that regional DHA signaling is independent of extracellular calcium, and likely mediated by a calcium-independent phospholipase A(2) (iPLA(2)). Studies in mice in which iPLA(2)-VIA (β) was knocked out confirmed that this enzyme is critical for baseline and muscarinic cholinergic signaling involving DHA. Thus, quantitative imaging of DHA incorporation from plasma into brain can be used as an in vivo biomarker of brain DHA metabolism and neurotransmission.
Authors:
Stanley I Rapoport; Epolia Ramadan; Mireille Basselin
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural; Review     Date:  2011-06-15
Journal Detail:
Title:  Prostaglandins & other lipid mediators     Volume:  96     ISSN:  1098-8823     ISO Abbreviation:  Prostaglandins Other Lipid Mediat.     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-14     Completed Date:  2012-04-17     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  9808648     Medline TA:  Prostaglandins Other Lipid Mediat     Country:  United States    
Other Details:
Languages:  eng     Pagination:  109-13     Citation Subset:  IM    
Copyright Information:
Published by Elsevier Inc.
Affiliation:
Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Autoradiography / methods*
Biological Markers / analysis
Brain Chemistry*
Docosahexaenoic Acids / metabolism*,  pharmacology
Humans
Injections, Intravenous
Mice
Mice, Knockout
N-Methylaspartate / metabolism,  pharmacology
Neuroprotective Agents / metabolism,  pharmacology
Phospholipases A2 / metabolism*
Positron-Emission Tomography
Radionuclide Imaging / methods*
Rats
Rats, Inbred Strains
Signal Transduction / drug effects,  physiology*
Synaptic Transmission / drug effects,  physiology*
alpha-Linolenic Acid / metabolism
Grant Support
ID/Acronym/Agency:
Z01 AG000134-25/AG/NIA NIH HHS; Z01 AG000148-09/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Neuroprotective Agents; 25167-62-8/Docosahexaenoic Acids; 463-40-1/alpha-Linolenic Acid; 6384-92-5/N-Methylaspartate; EC 3.1.1.4/Phospholipases A2
Comments/Corrections

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