| Title |
Mutant Ataxin-3 with an Abnormally Expanded Polyglutamine Chain Disrupts Dendritic Development and Metabotropic Glutamate Receptor Signaling in Mouse Cerebellar Purkinje Cells
|
|---|---|
| Published in |
The Cerebellum, August 2013
|
| DOI | 10.1007/s12311-013-0516-5 |
| Pubmed ID | |
| Authors |
Ayumu Konno, Anton N. Shuvaev, Noriko Miyake, Koichi Miyake, Akira Iizuka, Serina Matsuura, Fathul Huda, Kazuhiro Nakamura, Shigeru Yanagi, Takashi Shimada, Hirokazu Hirai |
| Abstract |
Spinocerebellar ataxia type 3 (SCA3) is caused by the abnormal expansion of CAG repeats within the ataxin-3 gene. Previously, we generated transgenic mice (SCA3 mice) that express a truncated form of ataxin-3 containing abnormally expanded CAG repeats specifically in cerebellar Purkinje cells (PCs). Here, we further characterize these SCA3 mice. Whole-cell patch-clamp analysis of PCs from advanced-stage SCA3 mice revealed a significant decrease in membrane capacitance due to poor dendritic arborization and the complete absence of metabotropic glutamate receptor subtype1 (mGluR1)-mediated retrograde suppression of synaptic transmission at parallel fiber terminals, with an overall preservation of AMPA receptor-mediated fast synaptic transmission. Because these cerebellar phenotypes are reminiscent of retinoic acid receptor-related orphan receptor α (RORα)-defective staggerer mice, we examined the levels of RORα in the SCA3 mouse cerebellum by immunohistochemistry and found a marked reduction of RORα in the nuclei of SCA3 mouse PCs. To confirm that the defects in SCA3 mice were caused by postnatal deposition of mutant ataxin-3 in PCs, not by genome disruption via transgene insertion, we tried to reduce the accumulation of mutant ataxin-3 in developing PCs by viral vector-mediated expression of CRAG, a molecule that facilitates the degradation of stress proteins. Concomitant with the removal of mutant ataxin-3, CRAG-expressing PCs had greater numbers of differentiated dendrites compared to non-transduced PCs and exhibited retrograde suppression of synaptic transmission following mGluR1 activation. These results suggest that postnatal nuclear accumulation of mutant ataxin-3 disrupts dendritic differentiation and mGluR-signaling in SCA3 mouse PCs, and this disruption may be caused by a defect in a RORα-driven transcription pathway. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Science communicators (journalists, bloggers, editors) | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 52 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Brazil | 1 | 2% |
| Unknown | 51 | 98% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 18 | 35% |
| Student > Master | 10 | 19% |
| Researcher | 7 | 13% |
| Student > Bachelor | 3 | 6% |
| Professor | 2 | 4% |
| Other | 3 | 6% |
| Unknown | 9 | 17% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 23 | 44% |
| Neuroscience | 9 | 17% |
| Biochemistry, Genetics and Molecular Biology | 4 | 8% |
| Medicine and Dentistry | 4 | 8% |
| Immunology and Microbiology | 1 | 2% |
| Other | 1 | 2% |
| Unknown | 10 | 19% |
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 14 March 2017.
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#14,262,465
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Outputs from The Cerebellum
#342
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Outputs of similar age
#108,080
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Outputs of similar age from The Cerebellum
#9
of 21 outputs
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