title: Imaging brain signal transduction and metabolism via arachidonic and docosahexaenoic acid in animals and humans.
abstract: 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.
authors.affiliation: Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Mireille
authors.initials: M
authors.lastname: Basselin
authors.forename: Epolia
authors.initials: E
authors.lastname: Ramadan
authors.forename: Stanley I
authors.initials: SI
authors.lastname: Rapoport
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use; D016718:Arachidonic Acid / Q000378:metabolism*; D001345:Autoradiography; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D001931:Brain Mapping; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D059906:Neuroimaging; D054467:Phospholipases A2 / Q000378:metabolism; D011877:Radionuclide Imaging; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D000928:Antidepressive Agents; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D054467:Phospholipases A2