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Papers In Press, published online ahead of print March 1, 2009
J. Lipid Res., doi:10.1194/jlr.M800382-JLR200

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Journal of Lipid Research, Vol. 50, 405-411, March 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Perinatal n-3 fatty acid deficiency selectively reduces myo-inositol levels in the adult rat PFC: an in vivo ¹H-MRS study^*,

Robert K. McNamara^1,*, Jessica Able^*, Ronald Jandacek, Therese Rider, Patrick Tso and Diana M. Lindquist

^* Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, OH 45267
Department of Pathology, University of Cincinnati, Cincinnati OH 45237
Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati OH 45267

^* This work was supported in part by National Institute of Mental Health grants MH073704 and MH074858 to R.K.M., and DK59630 to P.T.

The online version of this article (available at http://www.jlr.org) contains supplementary data in the form of one table.

Published, JLR Papers in Press, September 18, 2008.

¹ To whom correspondence should be addressed. e-mail: robert.mcnamara{at}psychiatry.uc.edu

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 (¹H-MRS). To generate graded deficits in PFC docosahexaenoic acid (22:6n-3) (DHA) composition, perinatal and postweaning -linolenic acid (18:3n-3) (ALA) deficiency models were used. Adult male rats were scanned in a 7T Bruker Biospec system and a ¹H-MRS spectrum acquired from the bilateral medial PFC. Rats were then challenged with SKF83959, a selective agonist at phosphoinositide (PI)-coupled dopamine D₁ 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.

Supplementary key words proton magnetic resonance spectroscopy • omega-3 fatty acids • docosahexaenoic acid • DHA • Myo-inositol • N-acetyl aspartate • prefrontal cortex

Abbreviations: AA, arachidonic acid (20:4n-6); ALA, alpha-linolenic acid (18:3n-3); Cho, choline; Cr, creatine; DHA, docosahexaenoic acid (22:6n-3); DPA, docosapentaenoic acid (22:5n-6); Glx, glutamine and glutamate; ¹H-MRS, proton magnetic resonance spectroscopy; MARCKS, myristoylated alanine-rich C kinase substrate; mI, myo-inositol; NAA, N-acetyl aspartate; PFC, prefrontal cortex; PI, phosphoinositide; PLC, phospholipase C; Tau, taurine

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