title: Cerebellar long-term depression is deficient in Niemann-Pick type C disease mice.
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.
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.
authors.forename: Cheng-Long
authors.initials: CL
authors.lastname: Sun
authors.forename: Li-Da
authors.initials: LD
authors.lastname: Su
authors.forename: Qiong
authors.initials: Q
authors.lastname: Li
authors.forename: Xin-Xin
authors.initials: XX
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Shen
mesh_terms: D000241:Adenosine / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002531:Cerebellum / Q000473:pathology*; D055724:Electrophysiological Phenomena; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000502:physiology*; D052556:Niemann-Pick Disease, Type C / Q000235:genetics / Q000473:pathology*; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000502:physiology; D011689:Purkinje Cells / Q000502:physiology; D043682:Receptor, Adenosine A1 / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D009435:Synaptic Transmission / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D043682:Receptor, Adenosine A1; D005680:gamma-Aminobutyric Acid; D000255:Adenosine Triphosphate; D000241:Adenosine