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|Title:||THE FULL BRAIN DISTRIBUTION OF NEUTRAL SPHINGOMYELINASE 2 AND ITS ROLE IN THE STRIATUM||Authors:||TAN HUI RU LAURA||Keywords:||Neutral Sphingomyelinase 2, SMPD3, Striatum, Distribution, Balance, NSM2||Issue Date:||23-Jun-2016||Citation:||TAN HUI RU LAURA (2016-06-23). THE FULL BRAIN DISTRIBUTION OF NEUTRAL SPHINGOMYELINASE 2 AND ITS ROLE IN THE STRIATUM. ScholarBank@NUS Repository.||Abstract:||Sphingomyelinases (SMases) play important roles in the brain due to their ability to alter neuronal lipid membrane composition and generate ceramide, a key regulator of many cellular signaling pathways. Irregularities in their expression or function can result in disturbance to sphingolipid homeostasis and altered neuronal membrane composition that could result in physiological dysfunction in various parts of the brain. However, little information is known about the relative distribution and physiological functions of SMases in specific brain regions. Therefore, the present study was carried out to examine the differential distribution and localization of SMase isoforms in different regions of the brain. N-SMase2 was singled out from the full brain real-time RT-PCR results due to its highest expression mRNA expression in the striatum, as well as its prominence in many pathophysiologies in the brain. Western blot confirmed the real-time RT-PCR results, showing a 71 kDa band detected the strongest at the striatum. N-SMase2 was found to be localized heavily in the caudate nucleus of the striatum, with electron microscopy findings indicating that N-SMase2 is present at the post-synaptic terminals of glutamatergic dendrites. A functional role for N-SMase2 in the striatum was then established by using a N-SMase2 inhibitor. Inhibition of N-SMase2 resulted in a loss of motor coordination and balance, a reduction in acoustic startle reflex as well as an improvement in sensorimotor gating. Together, the results demonstrate several important functional roles N-SMase2 plays in the striatum.||URI:||http://scholarbank.nus.edu.sg/handle/10635/132119|
|Appears in Collections:||Master's Theses (Open)|
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