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Neural symptoms in a gene knockout mouse model of Sjögren-Larsson syndrome are associated with a decrease in 2-hydroxygalactosylceramide.
- Source :
-
FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2019 Jan; Vol. 33 (1), pp. 928-941. Date of Electronic Publication: 2018 Aug 07. - Publication Year :
- 2019
-
Abstract
- Insulation by myelin lipids is essential to fast action potential conductivity: changes in their quality or amount can cause several neurologic disorders. Sjögren-Larsson syndrome (SLS) is one such disorder, which is caused by mutations in the fatty aldehyde dehydrogenase ALDH3A2. To date, the molecular mechanism underlying SLS pathology has remained unknown. In this study, we found that Aldh3a2 is expressed in oligodendrocytes and neurons in the mouse brain, and neurons of Aldh3a2 knockout (KO) mice exhibited impaired metabolism of the long-chain base, a component of sphingolipids. Aldh3a2 KO mice showed several abnormalities corresponding to SLS symptoms in behavioral tests, including increased paw slips on a balance beam and light-induced anxiety. In their brain tissue, 2-hydroxygalactosylceramide, an important lipid for myelin function and maintenance, was reduced by the inactivation of fatty acid 2-hydroxylase. Our findings provide important new insights into the molecular mechanisms responsible for neural pathogenesis caused by lipid metabolism abnormalities.-Kanetake, T., Sassa, T., Nojiri, K., Sawai, M., Hattori, S., Miyakawa, T., Kitamura, T., Kihara, A. Neural symptoms in a gene knockout mouse model of Sjögren-Larsson syndrome are associated with a decrease in 2-hydroxygalactosylceramide.
- Subjects :
- Aldehyde Oxidoreductases genetics
Aldehyde Oxidoreductases metabolism
Animals
Anxiety metabolism
Depression metabolism
Galactosylceramides genetics
Humans
Light
Lipid Metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Motor Activity
Sjogren-Larsson Syndrome genetics
Sjogren-Larsson Syndrome metabolism
Behavior, Animal
Galactosylceramides deficiency
Sjogren-Larsson Syndrome physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 1530-6860
- Volume :
- 33
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology
- Publication Type :
- Academic Journal
- Accession number :
- 30085884
- Full Text :
- https://doi.org/10.1096/fj.201800291R