title: Lipid abnormalities in succinate semialdehyde dehydrogenase (Aldh5a1-/-) deficient mouse brain provide additional evidence for myelin alterations.
abstract: Earlier work from our laboratory provided evidence for myelin abnormalities (decreased quantities of proteins associated with myelin compaction, decreased sheath thickness) in cortex and hippocampus of Aldh5a1(-/-) mice, which have a complete ablation of the succinate semialdehyde dehydrogenase protein [E.A. Donarum, D.A. Stephan, K. Larkin, E.J. Murphy, M. Gupta, H. Senephansiri, R.C. Switzer, P.L. Pearl, O.C. Snead, C. Jakobs, K.M. Gibson, Expression profiling reveals multiple myelin alterations in murine succinate semialdehyde dehydrogenase deficiency, J. Inher. Metab. Dis. 29 (2006) 143-156]. In the current report, we have extended these findings via comprehensive analysis of brain phospholipid fractions, including quantitation of fatty acids in individual phospholipid subclasses and estimation of hexose-ceramide in Aldh5a1(-/-) brain. In comparison to wild-type littermates (Aldh5a1(+/+)), we detected a 20% reduction in the ethanolamine glycerophospholipid content of Aldh5a1(-/-)mice, while other brain phospholipids (choline glycerophospholipid, phosphatidylserine and phosphatidylinositol) were within normal limits. Analysis of individual fatty acids in each of these fractions revealed consistent alterations in n-3 fatty acids, primarily increased 22:6n-3 levels (docosahexaenoic acid; DHA). In the phosphatidyl serine fraction there were marked increases in the proportions of polyunsaturated fatty acids with corresponding decreases of monounsaturated fatty acids. Interestingly, the levels of hexose-ceramide (glucosyl- and galactosylceramide, principal myelin cerebrosides) were decreased in Aldh5a1(-/-) brain tissue (one-tailed t test, p=0.0449). The current results suggest that lipid and myelin abnormalities in this animal may contribute to the pathophysiology.
authors.affiliation: Department of Pharmacology, Physiology, and Therapeutics, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58203, USA.
authors.forename: G
authors.initials: G
authors.lastname: Barcelo-Coblijn
authors.forename: E J
authors.initials: EJ
authors.lastname: Murphy
authors.forename: K
authors.initials: K
authors.lastname: Mills
authors.forename: B
authors.initials: B
authors.lastname: Winchester
authors.forename: C
authors.initials: C
authors.lastname: Jakobs
authors.forename: O C
authors.initials: OC
authors.lastname: Snead
authors.forename: K M
authors.initials: KM
authors.lastname: Gibson
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism*; D050644:Succinate-Semialdehyde Dehydrogenase / Q000235:genetics / Q000378:metabolism*
chemical_list: D005227:Fatty Acids; D010743:Phospholipids; D050644:Succinate-Semialdehyde Dehydrogenase