Modulation of phosphoinositide-protein kinase C signal transduction by omega-3 fatty acids: implications for the pathophysiology and treatment of recurrent neuropsychiatric illness.
The phosphoinositide (PI)-protein kinase C (PKC) signal transduction pathway is initiated by pre- and postsynaptic Galphaq-coupled receptors, and regulates several clinically relevant neurochemical events, including neurotransmitter release efficacy, monoamine receptor function and trafficking, monoamine transporter function and trafficking, axonal myelination, and gene expression. Mounting evidence for PI-PKC signaling hyperactivity in the peripheral (platelets) and central (premortem and postmortem brain) tissues of patients with schizophrenia, bipolar disorder, and major depressive disorder, coupled with evidence that PI-PKC signal transduction is down-regulated in rat brain following chronic, but not acute, treatment with antipsychotic, mood-stabilizer, and antidepressant medications, suggest that PI-PKC hyperactivity is central to an underlying pathophysiology. Evidence that membrane omega-3 fatty acids act as endogenous antagonists of the PI-PKC signal transduction pathway, coupled with evidence that omega-3 fatty acid deficiency is observed in peripheral and central tissues of patients with schizophrenia, bipolar disorder, and major depressive disorder, support the hypothesis that omega-3 fatty acid deficiency may contribute to elevated PI-PKC activity in these illnesses. The data reviewed in this paper outline a potential molecular mechanism by which omega-3 fatty acids could contribute to the pathophysiology and treatment of recurrent neuropsychiatric illness.
McNamara
Robert K
RK
Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0559, USA. robert.mcnamara@psychiatry.uc.edu
Ostrander
Michelle
M
Abplanalp
William
W
Richtand
Neil M
NM
Benoit
Stephen C
SC
Clegg
Debbie J
DJ
D000818:Animals; D005227:Fatty Acids / Q000502:physiology; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008563:Membrane Lipids / Q000502:physiology; D001523:Mental Disorders / Q000188:drug therapy* / Q000209:etiology*; D008954:Models, Biological; D010716:Phosphatidylinositols / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D012008:Recurrence; D015398:Signal Transduction / Q000187:drug effects*
D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D008563:Membrane Lipids; D010716:Phosphatidylinositols; D011493:Protein Kinase C