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Inbred C57BL/6J and DBA/2J Mouse Strains Exhibit Constitutive Differences in Regional Brain Fatty Acid Composition

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Lipids

Abstract

Major behavioral and neurochemical features observed between inbred C57BL/6 and DBA/2 mouse strains can be reproduced within rodent strains following dietary-induced reductions in brain docosahexaenoic acid (DHA, 22:6n-3) composition. It was therefore hypothesized that C57BL/6 and DBA/2 mice exhibit constitutive differences in brain DHA composition that are independent of diet. To test this, adult C57BL/6J and DBA/2J prefrontal cortex, hippocampus, ventral striatum, and midbrain fatty acid composition was determined by gas chromatography. After correction for multiple comparisons, C57BL/6J mice exhibited significantly lower DHA composition in the hippocampus and ventral striatum, but not prefrontal cortex or midbrain, and significantly greater regional arachidonic acid (ARA, 20:4n-6):DHA ratios, relative to DBA/2J mice. C57BL/6J mice also exhibited significantly lower regional adrenic acid (ADA, 22:4n-6) composition, and a significantly smaller ADA:ARA ratio, relative to DBA/2J mice. C57BL/6J mice exhibited significantly smaller oleic acid:stearic acid ratio in the hippocampus and ventral striatum relative to DBA/2J mice. Among all mice, DHA composition was positively correlated with the ADA:ARA ratio and inversely correlated with the oleic acid:stearic acid ratio. These data demonstrate that inbred C57BL/6J and DBA/2J mouse strains exhibit constitutive and region-specific differences in fatty acid composition independent of diet, and suggest that heritable genetic factors are an important determinant of central fatty acid composition.

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References

  1. Jones CR, Arai T, Bell JM, Rapoport SI (1996) Preferential in vivo incorporation of [3H]arachidonic acid from blood in rat brain synaptosomal fractions before and after cholinergic stimulation. J Neurochem 67:822–829

    PubMed  CAS  Google Scholar 

  2. Suzuki H, Manabe S, Wada O, Crawford MA (1997) Rapid incorporation of docosahexaenoic acid from dietary sources into brain microsomal, synaptosomal and mitochondrial membranes in adult mice. Int J Vitam Nutr Res 67:272–278

    PubMed  CAS  Google Scholar 

  3. Lee CH, Hajra AK (1991) Molecular species of diacylglycerols and phosphoglycerides and the postmortem changes in the molecular species of diacylglycerols in rat brains. J Neurochem 56:370–379

    Article  PubMed  CAS  Google Scholar 

  4. McNamara RK, Ostrander M, Abplanalp W, Richtand NM, Benoit SC, Clegg DJ (2006) Modulation of phosphoinositide-protein kinase C signal transduction by omega–3 fatty acids: implications for the pathophysiology and treatment of recurrent neuropsychiatric illness. Prostaglandins Leukot Essent Fatty Acids 75:237–257

    Article  PubMed  CAS  Google Scholar 

  5. Farooqui AA, Horrocks LA, Farooqui T (2007) Modulation of inflammation in brain: a matter of fat. J Neurochem 101:577–599

    Article  PubMed  CAS  Google Scholar 

  6. Chalon S (2006) Omega–3 fatty acids and monoamine neurotransmission. Prostaglandins Leukot Essent Fatty Acids 75:259–269

    Article  PubMed  CAS  Google Scholar 

  7. Fedorova I, Salem N Jr (2006) Omega-3 fatty acids and rodent behavior. Prostaglandins Leukot Essent Fatty Acids 75:271–289

    Article  PubMed  CAS  Google Scholar 

  8. McNamara RK, Jandacek R, Rider T, Tso P, Hahn CG, Richtand NM, Stanford KE (2007) Abnormalities in the fatty acid composition of the postmortem orbitofrontal cortex of schizophrenic patients: gender differences and partial normalization with antipsychotic medications. Schizophr Res 91:37–50

    Article  PubMed  Google Scholar 

  9. McNamara RK, Jandacek R, Rider T, Tso P, Stanford K, Hahn C-G, Richtand NM (2008) Deficits in docosahexaenoic acid and associated elevations in the metabolism of arachidonic acid and saturated fatty acids in the postmortem orbitofrontal cortex of patients with bipolar disorder. Psychiatric Res 160:285–299

    Article  CAS  Google Scholar 

  10. McNamara RK, Hahn CG, Jandacek R, Rider T, Tso P, Stanford KE, Richtand NM (2007) Selective deficits in the omega-3 fatty acid docosahexaenoic acid in the postmortem orbitofrontal cortex of patients with major depressive disorder. Biol Psychiatry 62:17–24

    Article  PubMed  CAS  Google Scholar 

  11. Igarashi M, Ma K, Chang L, Bell JM, Rapoport SI (2007) Dietary n-3 PUFA deprivation for 15 weeks upregulates elongase and desaturase expression in rat liver but not brain. J Lipid Res 48:2463–2470

    Article  PubMed  CAS  Google Scholar 

  12. Sprecher H, Chen Q, Yin FQ (1999) Regulation of the biosynthesis of 22:5n–6 and 22:6n–3: a complex intracellular process. Lipids 34:S153–S156

    Article  PubMed  CAS  Google Scholar 

  13. Ntambi JM, Miyazaki M (2004) Regulation of stearoyl-CoA desaturases and role in metabolism. Prog Lipid Res 43:91–104

    Article  PubMed  CAS  Google Scholar 

  14. Ntambi JM (1999) Regulation of stearoyl-CoA desaturase by polyunsaturated fatty acids and cholesterol. J Lipid Res 40:1549–1558

    PubMed  CAS  Google Scholar 

  15. Leonard AE, Bobik EG, Dorado J, Kroeger PE, Chuang LT, Thurmond JM, Parker-Barnes JM, Das T, Huang YS, Mukerji P (2000) Cloning of a human cDNA encoding a novel enzyme involved in the elongation of long-chain polyunsaturated fatty acids. Biochem J 350:765–770

    Article  PubMed  CAS  Google Scholar 

  16. Marquardt A, Stöhr H, White K, Weber BH (2000) cDNA cloning, genomic structure, and chromosomal localization of three members of the human fatty acid desaturase family. Genomics 66:175–183

    Article  PubMed  CAS  Google Scholar 

  17. Zhang L, Ge L, Parimoo S, Stenn K, Prouty SM (1999) Human stearoyl-CoA desaturase: alternative transcripts generated from a single gene by usage of tandem polyadenylation sites. Biochem J 340:255–264

    Article  PubMed  CAS  Google Scholar 

  18. Hamilton JA (2007) New insights into the roles of proteins and lipids in membrane transport of fatty acids. Prostaglandins Leukot Essent Fatty Acids 77:355–361

    Article  PubMed  CAS  Google Scholar 

  19. Malerba G, Schaeffer L, Xumerle L, Klopp N, Trabetti E, Biscuola M, Cavallari U, Galavotti R, Martinelli N, Guarini P, Girelli D, Olivieri O, Corrocher R, Heinrich J, Pignatti PF, Illig T (2008) SNPs of the FADS gene cluster are associated with polyunsaturated fatty acids in a cohort of patients with cardiovascular disease. Lipids 43:289–299

    Article  PubMed  CAS  Google Scholar 

  20. Martinez M (1992) Abnormal profiles of polyunsaturated fatty acids in the brain, liver, kidney and retina of patients with peroxisomal disorders. Brain Res 583:171–182

    PubMed  CAS  Google Scholar 

  21. Matsuzono Y, Kinoshita N, Tamura S, Shimozawa N, Hamasaki M, Ghaedi K, Wanders RJ, Suzuki Y, Kondo N, Fujiki Y (1999) Human PEX19: cDNA cloning by functional complementation, mutation analysis in a patient with Zellweger syndrome, and potential role in peroxisomal membrane assembly. Proc Natl Acad Sci USA 96:2116–2121

    Article  PubMed  CAS  Google Scholar 

  22. Schaeffer L, Gohlke H, Müller M, Heid IM, Palmer LJ, Kompauer I, Demmelmair H, Illig T, Koletzko B, Heinrich J (2006) Common genetic variants of the FADS1 FADS2 gene cluster and their reconstructed haplotypes are associated with the fatty acid composition in phospholipids. Hum Mol Genet 15:1745–1756

    Article  PubMed  CAS  Google Scholar 

  23. Bowers BJ, Christensen SC, Pauley JR, Paylor R, Yuva L, Dunbar SE, Wehner JM (1995) Protein and molecular characterization of hippocampal protein kinase C in C57BL/6 and DBA/2 mice. J Neurochem 64:2737–2746

    PubMed  CAS  Google Scholar 

  24. Paylor R, Tracy R, Wehner J, Rudy JW (1994) DBA/2 and C57BL/6 mice differ in contextual fear but not auditory fear conditioning. Behav Neurosci 108:810–817

    Article  PubMed  CAS  Google Scholar 

  25. Ng GY, O’Dowd BF, George SR (1994) Genotypic differences in brain dopamine receptor function in the DBA/2J and C57BL/6J inbred mouse strains. Eur J Pharmacol 269:349–364

    Article  PubMed  CAS  Google Scholar 

  26. Ventura R, Alcaro A, Cabib S, Conversi D, Mandolesi L, Puglisi-Allegra S (2004) Dopamine in the medial prefrontal cortex controls genotype-dependent effects of amphetamine on mesoaccumbens dopamine release and locomotion. Neuropsychopharmacology 29:72–80

    Article  PubMed  CAS  Google Scholar 

  27. Cabib S, Puglisi-Allegra S, Ventura R (2002) The contribution of comparative studies in inbred strains of mice to the understanding of the hyperactive phenotype. Behav Brain Res 130:103–109

    Article  PubMed  CAS  Google Scholar 

  28. Lucki I, Dalvi A, Mayorga AJ (2001) Sensitivity to the effects of pharmacologically selective antidepressants in different strains of mice. Psychopharmacology (Berl) 155:315–322

    Article  CAS  Google Scholar 

  29. Moriguchi T, Salem N Jr (2003) Recovery of brain docosahexaenoate leads to recovery of spatial task performance. J Neurochem 87:297–309

    Article  PubMed  CAS  Google Scholar 

  30. Delion S, Chalon S, Guilloteau D, Besnard JC, Durand G (1996) alpha-Linolenic acid dietary deficiency alters age-related changes of dopaminergic and serotoninergic neurotransmission in the rat frontal cortex. J Neurochem 66:1582–1591

    PubMed  CAS  Google Scholar 

  31. Zimmer L, Vancassel S, Cantagrel S, Breton P, Delamanche S, Guilloteau D, Durand G, Chalon S (2002) The dopamine mesocorticolimbic pathway is affected by deficiency in n–3 polyunsaturated fatty acids. Am J Clin Nutr 75:662–667

    PubMed  CAS  Google Scholar 

  32. Levant B, Radel JD, Carlson SE (2004) Decreased brain docosahexaenoic acid during development alters dopamine-related behaviors in adult rats that are differentially affected by dietary remediation. Behav Brain Res 152:49–57

    PubMed  CAS  Google Scholar 

  33. DeMar JC Jr, Ma K, Bell JM, Igarashi M, Greenstein D, Rapoport SI (2006) One generation of n–3 polyunsaturated fatty acid deprivation increases depression and aggression test scores in rats. J Lipid Res 47:172–180

    Article  PubMed  CAS  Google Scholar 

  34. McNamara RK, Sullivan J, Richtand NM (2008) Omega-3 fatty acid deficiency augments amphetamine-induced behavioral sensitization in adult mice: prevention by chronic lithium treatment. J Psychiatr Res 42:458–468

    Article  PubMed  Google Scholar 

  35. McNamara RK, Sullivan J, Richtand NM, Jandacek R, Rider T, Tso P, Campbell N, Lipton J (2008) Omega-3 fatty acid deficiency augments amphetamine-induced behavioral sensitization in adult DBA/2J mice: Relationship with ventral striatum dopamine concentrations. Synapse 62:725–735

    Article  PubMed  CAS  Google Scholar 

  36. Metcalfe LD, Schmitz AA, Pelka JR (1966) Rapid preparation of fatty acid esters from lipids for gas chromatographic analysis. Anal Chem 38:514–515

    Article  CAS  Google Scholar 

  37. Carrié I, Clément M, de Javel D, Francès H, Bourre JM (2000) Specific phospholipid fatty acid composition of brain regions in mice. Effects of n-3 polyunsaturated fatty acid deficiency and phospholipid supplementation. J Lipid Res 41:465–472

    PubMed  Google Scholar 

  38. Xiao Y, Huang Y, Chen ZY (2005) Distribution, depletion and recovery of docosahexaenoic acid are region-specific in rat brain. Br J Nutr 94:544–550

    Article  PubMed  CAS  Google Scholar 

  39. Wilson R, Bell MV (1993) Molecular species composition of glycerophospholipids from white matter of human brain. Lipids 28:13–17

    Article  PubMed  CAS  Google Scholar 

  40. Nguyen PV, Duffy SN, Young JZ (2000) Differential maintenance and frequency-dependent tuning of LTP at hippocampal synapses of specific strains of inbred mice. J Neurophysiol 84:2484–2493

    PubMed  CAS  Google Scholar 

  41. Gnegy ME, Hong P, Ferrell ST (1993) Phosphorylation of neuromodulin in rat striatum after acute and repeated, intermittent amphetamine. Mol Brain Res 20:289–298

    Article  PubMed  CAS  Google Scholar 

  42. Iwata S, Hewlett GH, Ferrell ST, Czernik AJ, Meiri KF, Gnegy ME (1996) Increased in vivo phosphorylation state of neuromodulin and synapsin I in striatum from rats treated with repeated amphetamine. J Pharmacol Exp Ther 278:1428–1434

    PubMed  CAS  Google Scholar 

  43. Narita M, Akai H, Nagumo Y, Sunagawa N, Hasebe K, Nagase H, Kita T, Hara C, Suzuki T (2004) Implications of protein kinase C in the nucleus accumbens in the development of sensitization to methamphetamine in rats. Neuroscience 127:941–948

    Article  PubMed  CAS  Google Scholar 

  44. Jakobsson A, Westerberg R, Jacobsson A (2006) Fatty acid elongases in mammals: their regulation and roles in metabolism. Prog Lipid Res 45:237–249

    Article  PubMed  CAS  Google Scholar 

  45. Rao JS, Ertley RN, DeMar JC Jr, Rapoport SI, Bazinet RP, Lee HJ (2007) Dietary n–3 PUFA deprivation alters expression of enzymes of the arachidonic and docosahexaenoic acid cascades in rat frontal cortex. Mol Psychiatry 12:151–157

    Article  PubMed  CAS  Google Scholar 

  46. McNamara RK, Liu Y, Jandacek R, Rider T, Tso P (2008) The aging human orbitofrontal cortex: Decreasing polyunsaturated fatty acid composition and associated increases in lipogenic gene expression and stearoyl-CoA desaturase activity. Prostaglandins Leukot Essent Fatty Acids 78:293–304

    Article  PubMed  CAS  Google Scholar 

  47. DeWille JW, Farmer SJ (1992) Postnatal dietary fat influences mRNAS involved in myelination. Dev Neurosci 14:61–68

    Article  PubMed  CAS  Google Scholar 

  48. Garbay B, Boiron-Sargueil F, Shy M, Chbihi T, Jiang H, Kamholz J, Cassagne C (1998) Regulation of oleoyl-CoA synthesis in the peripheral nervous system: demonstration of a link with myelin synthesis. J Neurochem 71:1719–1726

    Article  PubMed  CAS  Google Scholar 

  49. Kumar VB, Vyas K, Buddhiraju M, Alshaher M, Flood JF, Morley JE (1999) Changes in membrane fatty acids and delta–9 desaturase in senescence accelerated (SAMP8) mouse hippocampus with aging. Life Sci 65:1657–1662

    Article  PubMed  CAS  Google Scholar 

  50. Tanaka J, Okuma Y, Tomobe K, Nomura Y (2005) The age-related degeneration of oligodendrocytes in the hippocampus of the senescence-accelerated mouse (SAM) P8: a quantitative immunohistochemical study. Biol Pharm Bull 28:615–618

    Article  PubMed  CAS  Google Scholar 

  51. Green P, Gispan-Herman I, Yadid G (2005) Increased arachidonic acid concentration in the brain of Flinders Sensitive Line rats, an animal model of depression. J Lipid Res 46:1093–1096

    Article  PubMed  CAS  Google Scholar 

  52. Vancassel S, Blondeau C, Lallemand S, Cador M, Linard A, Lavialle M, Dellu-Hagedorn F (2007) Hyperactivity in the rat is associated with spontaneous low level of n–3 polyunsaturated fatty acids in the frontal cortex. Behav Brain Res 180:119–126

    Article  PubMed  CAS  Google Scholar 

  53. de Antueno RJ, Elliot M, Horrobin DF (1994) Liver delta 5 and delta 6 desaturase activity differs among laboratory rat strains. Lipids 29:327–331

    Article  PubMed  Google Scholar 

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Acknowledgments

This work was supported in part by National Institute of Mental Health grants MH073704 and MH074858 to R.K.M.

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Correspondence to Robert K. McNamara.

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McNamara, R.K., Able, J., Jandacek, R. et al. Inbred C57BL/6J and DBA/2J Mouse Strains Exhibit Constitutive Differences in Regional Brain Fatty Acid Composition. Lipids 44, 1–8 (2009). https://doi.org/10.1007/s11745-008-3244-8

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  • DOI: https://doi.org/10.1007/s11745-008-3244-8

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