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Substrate reduction reduces gangliosides in postnatal cerebrum-brainstem and cerebellum in GM1 gangliosidosis mice
- Source :
- Journal of Lipid Research; April 2005, Vol. 46 Issue: 4 p744-751, 8p
- Publication Year :
- 2005
-
Abstract
- II3NeuAc-GgOse4Cer (GM1) gangliosidosis is an incurable lysosomal storage disease caused by a deficiency in acid β-galactosidase (β-gal), resulting in the accumulation of ganglioside GM1 and its asialo derivative GgOse4Cer (GA1) in the central nervous system, primarily in the brain. In this study, we investigated the effects of N-butyldeoxygalacto-nojirimycin (NB-DGJ), an imino sugar that inhibits ganglioside biosynthesis, in normal C57BL/6J mice and in β-gal knockout (β-gal−/−) mice from postnatal day 9 (p-9) to p-15. This is a period of active cerebellar development and central nervous system (CNS) myelinogenesis in the mouse and would be comparable to late-stage embryonic and early neonatal development in humans. NB-DGJ significantly reduced total ganglioside and GM1 content in cerebrum-brainstem (C-BS) and in cerebellum of normal and β-gal−/−mice. NB-DGJ had no adverse effects on body weight or C-BS/cerebellar weight, water content, or thickness of the external cerebellar granule cell layer. Sphingomyelin was increased in C-BS and cerebellum, but no changes were found for cerebroside (a myelin-enriched glycosphingolipid), neutral phospholipids, or GA1 in the treated mice.
Details
- Language :
- English
- ISSN :
- 00222275 and 15397262
- Volume :
- 46
- Issue :
- 4
- Database :
- Supplemental Index
- Journal :
- Journal of Lipid Research
- Publication Type :
- Periodical
- Accession number :
- ejs7256093
- Full Text :
- https://doi.org/10.1194/jlr.M400411-JLR200