Lipid abnormalities in succinate semialdehyde dehydrogenase (Aldh5a1−/−) deficient mouse brain provide additional evidence for myelin alterations
- 作者：G. Barcelo-Coblijn ; E.J. Murphy ; K. Mills ; B. Winchester ; C. Jakobs ; O.C. Snead III ; K.M. Gibson
- 关键词：Succinate semialdehyde dehydrogenase (SSADH) ; Aldehyde dehydrogenase 5a1 (Aldh5a1) ; γ ; -hydroxybutyric acid ; γ ; -aminobutyric acid (GABA) ; Myelin ; Phospholipids ; Ethanolamine glycerophospholipid ; Ethanolamine plasmalogen ; Galactosylceramide
- 刊名：Biochimica et Biophysica Acta (BBA)/Molecular Basis of Disease
- 出版年：2007
- 期刊代码：19_09254439
- 类别：bio
- 出版时间：May 2007
- 卷：1772
- 期：5
- 页码：556-562
- 文件大小：188 K
摘要
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.