Reference - Detail
| RRC ID | 77821 |
|---|---|
| Author | Asakawa K, Handa H, Kawakami K. |
| Title | Dysregulated TDP-43 proteostasis perturbs excitability of spinal motor neurons during brainstem-mediated fictive locomotion in zebrafish. |
| Journal | Dev Growth Differ |
| Abstract |
Spinal motor neurons (SMNs) are the primary target of degeneration in amyotrophic lateral sclerosis (ALS). Degenerating motor neurons accumulate cytoplasmic TAR DNA-binding protein 43 (TDP-43) aggregates in most ALS cases. This SMN pathology can occur without mutation in the coding sequence of the TDP-43-encoding gene, TARDBP. Whether and how wild-type TDP-43 drives pathological changes in SMNs in vivo remains largely unexplored. In this study, we develop a two-photon calcium imaging setup in which tactile-evoked neural responses of motor neurons in the brainstem and spinal cord can be monitored using the calcium indicator GCaMP. We devise a piezo-assisted tactile stimulator that reproducibly evokes a brainstem descending neuron upon tactile stimulation of the head. A direct comparison between caudal primary motor neurons (CaPs) with or without TDP-43 overexpression in contiguous spinal segments demonstrates that CaPs overexpressing TDP-43 display attenuated Ca2+ transients during fictive escape locomotion evoked by the tactile stimulation. These results show that excessive amounts of TDP-43 protein reduce the neuronal excitability of SMNs and potentially contribute to asymptomatic pathological lesions of SMNs and movement disorders in patients with ALS. |
| Volume | 65(8) |
| Pages | 446-452 |
| Published | 2023-10-1 |
| DOI | 10.1111/dgd.12879 |
| PMID | 37452624 |
| MeSH | Amyotrophic Lateral Sclerosis* / genetics Amyotrophic Lateral Sclerosis* / metabolism Amyotrophic Lateral Sclerosis* / pathology Animals Calcium / metabolism DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism Humans Motor Neurons / metabolism Motor Neurons / pathology Proteostasis Spinal Cord Zebrafish / metabolism |
| IF | 1.723 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 15 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Zebrafish | hspGFFDMC130A, UAS:GFP, UAS:GCaMP7a, SAIGFF213A |