Lipid Abnormalities in Succinate Semialdehyde Dehydrogenase (Aldh5a1-/-) Deficient Mouse Brain Provide Additional Evidence for Myelin Alterations.
From: Department of Pharmacology, Physiology, and Therapeutics, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58203, USA.
Biochimica et biophysica acta
- Publish Date: May 2007
- ISSN: 0006-3002
- Volume: 1772
- Issue: 5
- Pages: 556-62
- Medium: Print
- Language: English
- Citation (JAMA): Barcelo-Coblijn G, Murphy E J, Mills K, et al. Lipid Abnormalities in Succinate Semialdehyde Dehydrogenase (Aldh5a1-/-) Deficient Mouse Brain Provide Additional Evidence for Myelin Alterations.. Biochim. Biophys. Acta May 2007;1772:556-62
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.
Mesh Headings (Keywords): Animals, Brain, Fatty Acids, Mice, Mice, Knockout, Myelin Sheath, Phospholipids, Succinate-Semialdehyde Dehydrogenase
Check for Full Text / PubMed Unique Identifier (PMID): 17300923
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