TY  - JOUR
A1  - Tejero, Rocio
A1  - Alsakkal, Mohammad
A1  - Hennlein, Luisa
A1  - Lopez-Cabello, Ana M.
A1  - Jablonka, Sibylle
A1  - Tabares, Lucia
T1  - Nifedipine ameliorates cellular differentiation defects of Smn-deficient motor neurons and enhances neuromuscular transmission in SMA mice
JF  - International Journal of Molecular Sciences
N2  - 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 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.
KW  - spinal muscular atrophy
KW  - motor neurons
KW  - synaptic transmission
KW  - neuromuscular junction
KW  - calcium channels
KW  - nifedipine
KW  - growth cone
KW  - axons
KW  - synaptic vesicles
KW  - postsynaptic potentials
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-313636
SN  - 1422-0067
VL  - 24
IS  - 8
ER  -