Transactive response DNA-binding protein of 43 kDa (TDP-43) is a nuclear
DNA/RNA-binding protein involved in gene transcription and mRNA processing. Recently,
TDP-43 has been found in the cytoplasmic inclusions observed in amyotrophic lateral sclerosis.
Substantial attention has been devoted to the toxic effects of the cytoplasmic TDP-43
aggregates, whereas the functional role of this protein remains poorly investigated. Interestingly,
TDP-43 could be localized in the synapse and affect synaptic plasticity and locomotion in
Drosophila. Here, we would like to understand if TDP-43 could modulate spinal cord plasticity
in a mouse model of neurotoxic motoneuron depletion. Therefore, the expression levels of TDP-
43 and synaptic proteins such as synapsin-I and the α-amino-3-hydroxy-5-methyl-4-
isoxazolepropionate (AMPA) receptor subunits GluR1, GluR2 and GluR4 were measured by
western blotting. By using multivariate regression models, protein expression levels were
correlated each other as well as with the motor performance. The results suggested that motor
performance could be linked to the expression of synapsin-I, and that the latter could depend on TDP-43, which in turn
could interact with AMPA receptors. In conclusion, our results suggest that TDP-43 is likely involved in the modulation
of synaptic plasticity. Given the increasing interest in mouse models of TDP-43 gain or loss of function in
neurodegenerative diseases, the elucidation of the role of TDP-43 in the spinal cord is mandatory. More generally, given
the recently increased knowledge about spinal cord plasticity, we postulate that the stimulation of the intrinsic plastic
potential of spinal cord would be a successful repairing strategy.
Keywords: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), cholera toxin-B saporin, motoneuron, mouse, spinal
cord, synapsin-I, synaptic plasticity, Transactive response DNA-binding protein of 43 kDa (TDP-43).
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