期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
卷 1772, 期 5, 页码 556-562出版社
ELSEVIER
DOI: 10.1016/j.bbadis.2006.12.008
关键词
succinate semialdehyde dehydrogenase (SSADH); aldehyde dehydrogenase 5al (Aldh5a1); gamma-hydroxybutyric acid; gamma-aminobutyric acid (GABA); myelin; phospholipids; ethanolamine glycerophospholipid; ethanolamine plasmalogen; galactosylceramide; docosohexaenoic acid (DHA)
资金
- NCRR NIH HHS [P20 RR017699, IP20-RR17699-01] Funding Source: Medline
- NINDS NIH HHS [R01 NS040270, NS 40270] Funding Source: Medline
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 Aldh5al(-/-) 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 Aldh5al(-/-) brain. In comparison to wild-type littermates (Aldh5a(+/+)), we detected a 20% reduction in the ethanolamine glycerophospholipid content of Aldh5al(-/-) 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 Aldh5al(-/-) 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. (C) 2007 Elsevier B.V. All rights reserved.
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