Dietary n-3 PUFA deprivation alters expression of enzymes of the arachidonic and docosahexaenoic acid cascades in rat frontal cortex.

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  • Additional Information
    • Source:
      Publisher: Nature Publishing Group Specialist Journals Country of Publication: England NLM ID: 9607835 Publication Model: Print-Electronic Cited Medium: Print ISSN: 1359-4184 (Print) Linking ISSN: 13594184 NLM ISO Abbreviation: Mol Psychiatry Subsets: MEDLINE
    • Publication Information:
      Publication: 2000- : Houndmills, Basingstoke, UK : Nature Publishing Group Specialist Journals
      Original Publication: Houndmills, Hampshire, UK ; New York, NY : Stockton Press, c1996-
    • Subject Terms:
      Arachidonic Acid/*metabolism ; Cyclooxygenase 1/*genetics ; Docosahexaenoic Acids/*metabolism ; Fatty Acids, Omega-3/*pharmacology ; Frontal Lobe/*enzymology; Animals ; Cyclooxygenase 1/metabolism ; Dietary Fats/pharmacology ; Enzyme Activation/drug effects ; Frontal Lobe/drug effects ; Gene Expression Regulation, Enzymologic/drug effects ; Group II Phospholipases A2 ; Male ; Phospholipases A/genetics ; Phospholipases A/metabolism ; Phospholipases A2 ; RNA, Messenger/metabolism ; Rats ; Rats, Long-Evans
    • Abstract:
      The enzymes that regulate the brain arachidonic acid (AA) cascade have been implicated in bipolar disorder and neuroinflammation. Fifteen weeks of dietary n-3 polyunsaturated fatty acid (PUFA) deprivation in rats decreases the concentration of docosahexaenoic acid (DHA) and increases its half-life within the brain. Based on this, we hypothesized that such dietary deprivation would decrease expression of enzymes responsible for the metabolic loss of DHA while increasing expression of those responsible for the metabolism of AA. Fifteen weeks of n-3 PUFA deprivation significantly decreased the activity, protein and mRNA expression of the DHA regulatory phospholipase A2 (PLA2), calcium-independent iPLA2, in rat frontal cortex. In contrast the activities, protein and mRNA levels of the AA selective calcium-dependent cytosolic phospholipase (cPLA2) and secretory sPLA2 were increased. Cyclooxygenase (COX)-1 protein but not mRNA was decreased in the n-3 PUFA-deprived rats whereas COX-2 protein and mRNA were increased. This study suggests that n-3 PUFA deprivation increases the half-live of brain DHA by downregulating iPLA2. The finding that n-3 PUFA deprivation increases cPLA2, sPLA2 and COX-2 is opposite to what has been reported after chronic administration of anti-manic agents to rats and suggests that n-3 PUFA deprivation may increase susceptibility to bipolar disorder.
    • Accession Number:
      0 (Dietary Fats)
      0 (Fatty Acids, Omega-3)
      0 (RNA, Messenger)
      25167-62-8 (Docosahexaenoic Acids)
      27YG812J1I (Arachidonic Acid)
      EC 1.14.99.1 (Cyclooxygenase 1)
      EC 3.1.1.32 (Phospholipases A)
      EC 3.1.1.4 (Group II Phospholipases A2)
      EC 3.1.1.4 (Phospholipases A2)
    • Publication Date:
      Date Created: 20060920 Date Completed: 20070327 Latest Revision: 20161124
    • Publication Date:
      20231215
    • Accession Number:
      10.1038/sj.mp.4001887
    • Accession Number:
      16983392