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|Title:||Enriched expression of neutral sphingomyelinase 2 in the striatum is essential for regulation of lipid raft content and motor coordination||Authors:||Tan, Laura Hui-Ru
Tan, Angela Jin-Rong
Chua, John Jia-En
Sze, Siu Kwan
Herr, Deron R.
|Keywords:||Science::Biological sciences||Issue Date:||2017||Source:||Tan, L. H.-R., Tan, A. J.-R., Ng, Y.-Y., Chua, J. J.-E., Chew, W.-S., Muralidharan, S., . . . Ong, W.-Y. (2018). Enriched expression of neutral sphingomyelinase 2 in the striatum is essential for regulation of lipid raft content and motor coordination. Molecular Neurobiology, 55(7), 5741-5756. doi:10.1007/s12035-017-0784-z||Journal:||Molecular Neurobiology||Abstract:||Sphingomyelinases are a family of enzymes that hydrolyze sphingomyelin to generate phosphocholine and ceramide. The brain distribution and function of neutral sphingomyelinase 2 (nSMase2) were elucidated in this study. nSMase2 mRNA expression was greatest in the striatum, followed by the prefrontal cortex, hippocampus, cerebellum, thalamus, brainstem, and olfactory bulb. The striatum had the highest level of nSMase2 protein expression, followed by the prefrontal cortex, thalamus, hippocampus, brainstem, and cerebellum. Dense immunolabeling was observed in the striatum, including the caudate-putamen, while moderately dense staining was found in the olfactory bulb and cerebral neocortex. Electron microscopy of the caudate-putamen showed nSMase2 immunoreaction product was present in small diameter dendrites or dendritic spines, that formed asymmetrical synapses with unlabeled axon terminals containing small round vesicles; and characteristics of glutamatergic axons. Lipidomic analysis of the striatum showed increase in long chain sphingomyelins, SM36:1 and SM38:1 after inhibition of nSMase activity. Quantitative proteomic analysis of striatal lipid raft fraction showed many proteins were downregulated by more than 2-fold after inhibition or antisense knockdown of nSMase; consistent with the notion that nSMase2 activity is important for aggregation or clustering of proteins in lipid rafts. Inhibition or antisense knockdown of nSMase2 in the caudate-putamen resulted in motor deficits in the rotarod and narrow beam tests; as well as decreased acoustic startle and improved prepulse inhibition of the startle reflex. Together, results indicate an important function of nSMase2 in the striatum.||URI:||https://hdl.handle.net/10356/139285||ISSN:||0893-7648||DOI:||10.1007/s12035-017-0784-z||Schools:||School of Biological Sciences||Rights:||© 2017 The Author(s). This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.||Fulltext Permission:||open||Fulltext Availability:||With Fulltext|
|Appears in Collections:||SBS Journal Articles|
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