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| Status |
Public on Aug 31, 2016 |
| Title |
Voluntary running triggers VGF-mediated oligodendrogenesis to prolong the lifespan of Snf2h-null ataxic mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Exercise enhances cognitive function and slows progressive neurodegenerative disease. While exercise promotes neurogenesis, oligodendrogenesis and adaptive myelination are also significant contributors to brain repair and brain health. Nonetheless, the molecular details underlying these effects remain poorly understood. Conditional ablation of the Snf2h gene (Snf2h cKO) impairs cerebellar development producing mice with poor motor function, progressive ataxia and death between postnatal day 25 to 45. Here we show that voluntary running induced an endogenous brain repair mechanism that resulted in a striking increase in hindbrain myelination and the long-term survival of Snf2h cKO mice. Further experiments identified the VGF growth factor as a major driver underlying this effect. VGF neuropeptides could promote oligodendrogenesis in vitro, while Snf2h cKO mice treated with full-length VGF-encoding adenoviruses obliterated the requirement of exercise for survival. Together, these results suggest that VGF delivery could represent a therapeutic strategy for cerebellar ataxia and other pathologies of the central nervous system.
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| Overall design |
4 samples per genotype in biological replicates (8 paired-end libraries)
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| Contributor(s) |
Alvarez-Saavedra M, De Repentigny Y, Yang D, O'Meara R, Yan K, E.Hashem L, Racacho L, Ioshikhes I, Bulman DE, Parks RJ, Kothary R, Picketts DJ |
| Citation(s) |
27732860 |
| |
| Submission date |
Aug 30, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Matias Alvarez-Saavedra |
| E-mail(s) |
malvarezsaavedra@yahoo.ca
|
| Organization name |
Ottawa Hospital Research Institute
|
| Department |
Regenerative Medicine
|
| Lab |
David Picketts
|
| Street address |
501 Smyth Road
|
| City |
Ottawa |
| State/province |
Ontario |
| ZIP/Postal code |
K1H8L1 |
| Country |
Canada |
| |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA340987 |
| SRA |
SRP083759 |
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