title: Brain Arachidonic Acid Incorporation and Turnover are not Altered in the Flinders Sensitive Line Rat Model of Human Depression.
abstract: Brain serotonergic signaling is coupled to arachidonic acid (AA)-releasing calcium-dependent phospholipase A2. Increased brain serotonin concentrations and disturbed serotonergic neurotransmission have been reported in the Flinders Sensitive Line (FSL) rat model of depression, suggesting that brain AA metabolism may be elevated. To test this hypothesis, (14)C-AA was intravenously infused to steady-state levels into control and FSL rats derived from the same Sprague-Dawley background strain, and labeled and unlabeled brain phospholipid and plasma fatty acid concentrations were measured to determine the rate of brain AA incorporation and turnover. Brain AA incorporation and turnover did not differ significantly between controls and FSL rats. Compared to controls, plasma unesterified docosahexaenoic acid was increased, and brain phosphatidylinositol AA and total lipid linoleic acid and n-3 and n-6 docosapentaenoic acid were significantly decreased in FSL rats. Several plasma esterified fatty acids differed significantly from controls. In summary, brain AA metabolism did not change in FSL rats despite reported increased levels of serotonin concentrations, suggesting possible post-synaptic dampening of serotonergic neurotransmission involving AA.
authors.affiliation: Brain Physiology and Metabolism Section, Laboratory of Neuroscience, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Helene
authors.initials: H
authors.lastname: Blanchard
authors.affiliation: Brain Physiology and Metabolism Section, Laboratory of Neuroscience, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Chang
authors.affiliation: Department of Psychiatric and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA.
authors.forename: Amir H
authors.initials: AH
authors.lastname: Rezvani
authors.affiliation: Brain Physiology and Metabolism Section, Laboratory of Neuroscience, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Stanley I
authors.initials: SI
authors.lastname: Rapoport
authors.affiliation: Department of Food Science and Technology, College of Agriculture and Environmental Sciences, University of California, RMI North, Room 3162, Davis, CA, USA. ataha@ucdavis.edu.
authors.forename: Ameer Y
authors.identifier: http://orcid.org/0000-0003-4611-7450
authors.initials: AY
authors.lastname: Taha
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism; D000465:Algorithms; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001923:Brain Chemistry / Q000235:genetics*; D003863:Depression / Q000235:genetics* / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D007700:Kinetics; D050356:Lipid Metabolism / Q000235:genetics; D008297:Male; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D009435:Synaptic Transmission
chemical_list: D000214:Acyl Coenzyme A; D005227:Fatty Acids; D010743:Phospholipids; D016718:Arachidonic Acid; D012701:Serotonin
keywords: Arachidonic acid; Brain lipid concentrations; Depression model; Fatty acids; Flinders Sensitive Line rat; Kinetic; Metabolism; Turnover