Abstract
Insulation by myelin lipids is essential to fast action potential conductivity: changes in their quality or amount can cause several neurologic disorders. Sjogren-Larsson syndrome (SLS) i s 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 neuronsinthemouse brain, and neurons of Aldh3a2knockout (KO)mice exhibitedimpaired metabolism ofthelongchain 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.
| Original language | English |
|---|---|
| Pages (from-to) | 928-941 |
| Number of pages | 14 |
| Journal | FASEB Journal |
| Volume | 33 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 01-01-2019 |
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All Science Journal Classification (ASJC) codes
- Biotechnology
- Biochemistry
- Molecular Biology
- Genetics
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Neural symptoms in a gene knockout mouse model of Sjogren-Larsson syndrome are associated with a decrease in 2-hydroxygalactosylceramide. / Kanetake, Tsukasa; Sassa, Takayuki; Nojiri, Koki; Sawai, Megumi; Takai, Satoko; Miyakawa, Tsuyoshi; Kitamura, Takuya; Kihara, Akio.
In: FASEB Journal, Vol. 33, No. 1, 01.01.2019, p. 928-941.Research output: Contribution to journal › Article
TY - JOUR
T1 - Neural symptoms in a gene knockout mouse model of Sjogren-Larsson syndrome are associated with a decrease in 2-hydroxygalactosylceramide
AU - Kanetake, Tsukasa
AU - Sassa, Takayuki
AU - Nojiri, Koki
AU - Sawai, Megumi
AU - Takai, Satoko
AU - Miyakawa, Tsuyoshi
AU - Kitamura, Takuya
AU - Kihara, Akio
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Insulation by myelin lipids is essential to fast action potential conductivity: changes in their quality or amount can cause several neurologic disorders. Sjogren-Larsson syndrome (SLS) i s 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 neuronsinthemouse brain, and neurons of Aldh3a2knockout (KO)mice exhibitedimpaired metabolism ofthelongchain 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.
AB - Insulation by myelin lipids is essential to fast action potential conductivity: changes in their quality or amount can cause several neurologic disorders. Sjogren-Larsson syndrome (SLS) i s 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 neuronsinthemouse brain, and neurons of Aldh3a2knockout (KO)mice exhibitedimpaired metabolism ofthelongchain 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.
UR - http://www.scopus.com/inward/record.url?scp=85059241498&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85059241498&partnerID=8YFLogxK
U2 - 10.1096/fj.201800291R
DO - 10.1096/fj.201800291R
M3 - Article
VL - 33
SP - 928
EP - 941
JO - FASEB Journal
JF - FASEB Journal
SN - 0892-6638
IS - 1
ER -