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.show moreshow less

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Metadaten
Author: Rocio Tejero, Mohammad Alsakkal, Luisa Hennlein, Ana M. Lopez-Cabello, Sibylle Jablonka, Lucia Tabares
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):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International