title: Relevance of neuronal and glial NPC1 for synaptic input to cerebellar Purkinje cells.
abstract: Niemann-Pick type C disease is a rare and ultimately fatal lysosomal storage disorder with variable neurologic symptoms. The disease-causing mutations concern NPC1 or NPC2, whose dysfunction entails accumulation of cholesterol in the endosomal-lysosomal system and the selective death of specific neurons, namely cerebellar Purkinje cells. Here, we investigated whether neurodegeneration is preceded by an imbalance of synaptic input to Purkinje cells and whether neuronal or glial absence of NPC1 has different impacts on synapses. To this end, we prepared primary cerebellar cultures from wildtype or NPC1-deficient mice that are glia-free and highly enriched with Purkinje cells. We report that lack of NPC1 in either neurons or glial cells did not affect the excitability of Purkinje cells, the formation of dendrites or their excitatory synaptic activity. However, simultaneous absence of NPC1 from neuronal and glial cells impaired the presynaptic input to Purkinje cells suggesting a cooperative effect of neuronal and glial NPC1 on synapses.
authors.affiliation: CNRS UPR 3212, University of Strasbourg, Institute of Cellular and Integrative Neurosciences (INCI), 67084 Strasbourg, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Buard
authors.affiliation: CNRS UPR 3212, University of Strasbourg, Institute of Cellular and Integrative Neurosciences (INCI), 67084 Strasbourg, France. Electronic address: fw-pfrieger@gmx.de.
authors.forename: Frank W
authors.initials: FW
authors.lastname: Pfrieger
mesh_terms: D000200:Action Potentials / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology*; D002784:Cholesterol / Q000378:metabolism; D018920:Coculture Techniques; D004558:Electric Stimulation; D053444:Inhibitory Postsynaptic Potentials / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D000077296:Niemann-Pick C1 Protein; D018408:Patch-Clamp Techniques; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011689:Purkinje Cells / Q000502:physiology*; D013569:Synapses / Q000235:genetics / Q000502:physiology*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; D000077296:Niemann-Pick C1 Protein; C106831:Npc1 protein, mouse; D011506:Proteins; D002784:Cholesterol
keywords: Cerebellum; Inborn error metabolism; Lysosomal storage disease; Neurodegenerative diseases; Neuroglia; Synaptogenesis