Perinatal n-3 fatty acid deficiency selectively reduces myo-inositol levels in the adult rat PFC: an in vivo (1)H-MRS study.
To investigate the effects of omega-3 fatty acid deficiency on phosphatidylinositol signaling in brain, myo-inositol (mI) concentrations were determined in the prefrontal cortex (PFC) of omega-3 fatty acid deficient rats by in vivo proton magnetic resonance spectroscopy ((1)H-MRS). To generate graded deficits in PFC docosahexaenoic acid (22:6n-3) (DHA) composition, perinatal and postweaning alpha-linolenic acid (18:3n-3) (ALA) deficiency models were used. Adult male rats were scanned in a 7T Bruker Biospec system and a (1)H-MRS spectrum acquired from the bilateral medial PFC. Rats were then challenged with SKF83959, a selective agonist at phosphoinositide (PI)-coupled dopamine D(1) receptors. Postmortem PFC fatty acid composition was determined by gas chromatography. Relative to controls, PFC DHA composition was significantly reduced in adult postweaning (-27%) and perinatal (-65%) ALA-deficiency groups. Basal PFC mI concentrations were significantly reduced in the perinatal deficiency group (-21%, P = 0.001), but not in the postweaning deficiency group (-1%, P = 0.86). Among all rats, DHA composition was positively correlated with mI concentrations and the mI/creatine (Cr) ratio. SKF83959 challenge significantly increased mI concentrations only in the perinatal deficiency group (+16%, P = 0.02). These data demonstrate that perinatal deficits in cortical DHA accrual significantly and selectively reduce mI concentrations and augment receptor-generated mI synthesis.
McNamara
Robert K
RK
Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, OH 45267. Electronic address: robert.mcnamara@psychiatry.uc.edu.
Able
Jessica
J
Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, OH 45267.
Jandacek
Ronald
R
Department of Pathology, University of Cincinnati, Cincinnati OH 45237.
Rider
Therese
T
Department of Pathology, University of Cincinnati, Cincinnati OH 45237.
Tso
Patrick
P
Department of Pathology, University of Cincinnati, Cincinnati OH 45237.
Lindquist
Diana M
DM
Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati OH 45267.
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D004281:Docosahexaenoic Acids / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000378:metabolism*; D005260:Female; D007294:Inositol / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D020318:Rats, Long-Evans; D017447:Receptors, Dopamine D1 / Q000819:agonists; D015398:Signal Transduction; D017962:alpha-Linolenic Acid / Q000008:administration & dosage / Q000172:deficiency
D015525:Fatty Acids, Omega-3; D017447:Receptors, Dopamine D1; D017962:alpha-Linolenic Acid; D004281:Docosahexaenoic Acids; D007294:Inositol; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C080703:SK&F 83959