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The Cerebellum
Published in: The Cerebellum 1/2011

01-03-2011

Cerebellar Long-term Depression is Deficient in Niemann–Pick Type C Disease Mice

Authors: Cheng-Long Sun, Li-Da Su, Qiong Li, Xin-Xin Wang, Ying Shen

Published in: The Cerebellum | Issue 1/2011

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Abstract

Niemann–Pick type C disease (NPC) is an autosomal recessive lipidosis characterized by progressive neurodegeneration. Although several studies have revealed unusual accumulation of unesterfied cholesterol in astrocytic lysosome of NPC, pathophysiological basis of cerebellar neuronal dysfunction remains unclear. We compared parallel fiber-Purkinje cell synaptic transmission and long-term depression (LTD) in +/+npc nih (npc +/+) and −/−npc nih (npc −/−) mice. Our data showed that adenosine A1 receptor agonists decreased parallel fiber excitatory postsynaptic current (EPSC) amplitude and mEPSC frequency while its antagonists increased EPSC amplitude and mEPSC frequency in wild type and mutant mice. Furthermore, parallel fiber LTD was deficient in npc −/− mice and supplement of adenosine triphosphate (ATP) rescued the impaired LTD. Taken together, these experiments suggest that synaptic strength and LTD are altered in npc −/− mice due to the decrease of ATP/adenosine release and deactivation of A1 receptors in parallel fiber terminals. The enhanced synaptic transmission and the decreased LTD might result in progressive neurotoxicity of Purkinje cells in npc −/− mice.
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Metadata
Title
Cerebellar Long-term Depression is Deficient in Niemann–Pick Type C Disease Mice
Authors
Cheng-Long Sun
Li-Da Su
Qiong Li
Xin-Xin Wang
Ying Shen
Publication date
01-03-2011
Publisher
Springer-Verlag
Published in
The Cerebellum / Issue 1/2011
Print ISSN: 1473-4222
Electronic ISSN: 1473-4230
DOI
https://doi.org/10.1007/s12311-010-0233-2

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