Nifedipine ameliorates cellular differentiation defects of Smn-deficient motor neurons and enhances neuromuscular transmission in SMA mice
Please always quote using this URN: urn:nbn:de:bvb:20-opus-313636
- In spinal muscular atrophy (SMA), mutations in or loss of the Survival Motor Neuron 1 (SMN1) gene reduce full-length SMN protein levels, which leads to the degeneration of a percentage of motor neurons. In mouse models of SMA, the development and maintenance of spinal motor neurons and the neuromuscular junction (NMJ) function are altered. Since nifedipine is known to be neuroprotective and increases neurotransmission in nerve terminals, we investigated its effects on cultured spinal cord motor neurons and motor nerve terminals of control andIn spinal muscular atrophy (SMA), mutations in or loss of the Survival Motor Neuron 1 (SMN1) gene reduce full-length SMN protein levels, which leads to the degeneration of a percentage of motor neurons. In mouse models of SMA, the development and maintenance of spinal motor neurons and the neuromuscular junction (NMJ) function are altered. Since nifedipine is known to be neuroprotective and increases neurotransmission in nerve terminals, we investigated its effects on cultured spinal cord motor neurons and motor nerve terminals of control and SMA mice. We found that application of nifedipine increased the frequency of spontaneous Ca\(^{2+}\) transients, growth cone size, cluster-like formations of Cav2.2 channels, and it normalized axon extension in SMA neurons in culture. At the NMJ, nifedipine significantly increased evoked and spontaneous release at low-frequency stimulation in both genotypes. High-strength stimulation revealed that nifedipine increased the size of the readily releasable pool (RRP) of vesicles in control but not SMA mice. These findings provide experimental evidence about the ability of nifedipine to prevent the appearance of developmental defects in SMA embryonic motor neurons in culture and reveal to which extent nifedipine could still increase neurotransmission at the NMJ in SMA mice under different functional demands.…
Author: | Rocio Tejero, Mohammad Alsakkal, Luisa Hennlein, Ana M. Lopez-Cabello, Sibylle Jablonka, Lucia Tabares |
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URN: | urn:nbn:de:bvb:20-opus-313636 |
Document Type: | Journal article |
Faculties: | Medizinische Fakultät / Institut für Klinische Neurobiologie |
Language: | English |
Parent Title (English): | International Journal of Molecular Sciences |
ISSN: | 1422-0067 |
Year of Completion: | 2023 |
Volume: | 24 |
Issue: | 8 |
Article Number: | 7648 |
Source: | International Journal of Molecular Sciences (2023) 24:8, 7648. https://doi.org/10.3390/ijms24087648 |
DOI: | https://doi.org/10.3390/ijms24087648 |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Tag: | axons; calcium channels; growth cone; motor neurons; neuromuscular junction; nifedipine; postsynaptic potentials; spinal muscular atrophy; synaptic transmission; synaptic vesicles |
Release Date: | 2023/12/06 |
Date of first Publication: | 2023/04/21 |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |