Please use this identifier to cite or link to this item: https://doi.org/10.1007/s12035-017-0784-z
Title: Enriched Expression of Neutral Sphingomyelinase 2 in the Striatum is Essential for Regulation of Lipid Raft Content and Motor Coordination
Authors: Tan, L.H.-R
Tan, A.J.-R
Ng, Y.-Y
Chua, J.J.-E 
Chew, W.-S 
Muralidharan, S 
Torta, F 
Dutta, B
Sze, S.K
Herr, D.R 
Ong, W.-Y 
Keywords: messenger RNA
neutral sphingomyelinase 2
sphingomyelin phosphodiesterase
unclassified drug
isoenzyme
messenger RNA
proteome
sphingolipid
sphingomyelin phosphodiesterase
adult
animal cell
animal experiment
animal tissue
antibody labeling
Article
brain cortex
brain stem
cerebellum
controlled study
corpus striatum
dendritic spine
dorsal striatum
down regulation
electron microscopy
enzyme activity
enzyme inhibition
gene expression
glutamatergic synapse
hippocampus
lipid analysis
lipid metabolism
lipid raft
lipidomics
male
motor coordination
nerve ending
nonhuman
olfactory bulb
prefrontal cortex
protein expression
proteomics
quantitative analysis
rat
rotarod test
thalamus
acoustic reflex
animal
corpus striatum
cytology
enzymology
gene expression regulation
gene knockdown
genetics
membrane microdomain
metabolism
motor activity
prepulse inhibition
startle reflex
ultrastructure
Wistar rat
Animals
Corpus Striatum
Gene Expression Regulation, Enzymologic
Gene Knockdown Techniques
Isoenzymes
Male
Membrane Microdomains
Motor Activity
Prepulse Inhibition
Proteome
Rats, Wistar
Reflex, Acoustic
Reflex, Startle
RNA, Messenger
Rotarod Performance Test
Sphingolipids
Sphingomyelin Phosphodiesterase
Issue Date: 2018
Publisher: Humana Press Inc.
Citation: Tan, L.H.-R, Tan, A.J.-R, Ng, Y.-Y, Chua, J.J.-E, Chew, W.-S, Muralidharan, S, Torta, F, Dutta, B, Sze, S.K, Herr, D.R, 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. ScholarBank@NUS Repository. https://doi.org/10.1007/s12035-017-0784-z
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. © 2017, The Author(s).
Source Title: Molecular Neurobiology
URI: https://scholarbank.nus.edu.sg/handle/10635/175111
ISSN: 0893-7648
DOI: 10.1007/s12035-017-0784-z
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