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- Title
Spinal muscular atrophy patient-derived motor neurons exhibit hyperexcitability.
- Authors
Liu, Huisheng; Lu, Jianfeng; Chen, Hong; Du, Zhongwei; Li, Xue-Jun; Zhang, Su-Chun
- Abstract
Spinal muscular atrophy (SMA) presents severe muscle weakness with limited motor neuron (MN) loss at an early stage, suggesting potential functional alterations in MNs that contribute to SMA symptom presentation. Using SMA induced pluripotent stem cells (iPSCs), we found that SMA MNs displayed hyperexcitability with increased membrane input resistance, hyperpolarized threshold, and larger action potential amplitude, which was mimicked by knocking down full length survival motor neuron (SMN) in non-SMA MNs. We further discovered that SMA MNs exhibit enhanced sodium channel activities with increased current amplitude and facilitated recovery, which was corrected by restoration of SMN1 in SMA MNs. Together we propose that SMN reduction results in MN hyperexcitability and impaired neurotransmission, the latter of which exacerbate each other via a feedback loop, thus contributing to severe symptoms at an early stage of SMA.
- Subjects
SPINAL muscular atrophy; MUSCLE weakness; MOTOR neurons; INDUCED pluripotent stem cells; NEURAL transmission; SODIUM channels; PATIENTS; PHYSIOLOGY
- Publication
Scientific Reports, 2015, p12189
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/srep12189