Early onset of ataxia in moonwalker mice is accompanied by complete ablation of type II unipolar brush cells and Purkinje cell dysfunction.Report as inadecuate




Early onset of ataxia in moonwalker mice is accompanied by complete ablation of type II unipolar brush cells and Purkinje cell dysfunction. - Download this document for free, or read online. Document in PDF available to download.

Reference: Sekerkov√°, G, Kim, JA, Nigro, MJ et al., (2013). Early onset of ataxia in moonwalker mice is accompanied by complete ablation of type II unipolar brush cells and Purkinje cell dysfunction. The Journal of neuroscience : the official journal of the Society for Neuroscience, 33 (50), 19689-19694.Citable link to this page:

 

Early onset of ataxia in moonwalker mice is accompanied by complete ablation of type II unipolar brush cells and Purkinje cell dysfunction.

Abstract: Transient receptor potential canonical cation channels (TRPC) are involved in many cellular activities, including neuronal synaptic transmission. These channels couple lipid metabolism, calcium homeostasis, and electrophysiological properties as they are calcium permeable and activated through the phospholipase C pathway and by diacylglycerol. The TRPC3 subunit is abundantly expressed in Purkinje cells (PCs), where it mediates slow metabotropic glutamate receptor-mediated synaptic responses. Recently, it has been shown that heterozygous moonwalker mice, which are a model of cerebellar ataxia, carry a dominant gain-of-function mutation (T635A) in the TRPC3 gene. This mutation leads to PC loss and dysmorphism, which have been suggested to cause the ataxia. However, the ataxic phenotype is present from a very early stage (before weaning), whereas PC loss does not appear until several months of age. Here we show that another class of cerebellar neurons, the type II unipolar brush cells (UBCs), express functional TRPC3 channels; intriguingly, these cells are ablated in moonwalker mice by 1 month of age. Additionally, we show that in moonwalker mice, intrinsic excitability of PCs is altered as early as 3 weeks after birth. We suggest that this altered excitability and the TRPC3-mediated loss of type II UBCs may both contribute to the ataxic phenotype of these mice and that different calcium handling in PCs and type II UBCs may account for the dramatic differences in sensitivity to the moonwalker mutation between these cell types.

Peer Review status:Peer ReviewedPublication status:PublishedVersion:Publishers CopyNotes:The publishers pdf has been made available for download thanks to the Society of Neuroscience who allow the work to become available to the public to copy, distribute, or display under a Creative Commons Attribution 4.0 International (CC BY 4.0) license

Bibliographic Details

Journal: The Journal of neuroscience : the official journal of the Society for Neurosciencesee more from them

Issue Date: 2013-12

pages:19689-19694Identifiers

Urn: uuid:89e46eb4-eae7-4ace-8417-0feef2f97a00

Source identifier: 443411

Eissn: 1529-2401

Doi: https://doi.org/10.1523/jneurosci.2294-13.2013

Issn: 0270-6474 Item Description

Type: Journal article;

Language: eng

Version: Publishers CopyKeywords: Animals Mice Cerebellum Purkinje Cells Neurons Cerebellar Ataxia Patch-Clamp Techniques Action Potentials TRPC Cation Channels Tiny URL: pubs:443411

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Author: Sekerkov√°, G - - - Kim, JA - - - Nigro, MJ - - - Becker, EB - institutionUniversity of Oxford Oxford, MSD, Physiology Anatomy an

Source: https://ora.ox.ac.uk/objects/uuid:89e46eb4-eae7-4ace-8417-0feef2f97a00



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