Calpain fosters the hyperexcitability of motoneurons after spinal cord injury and leads to spasticity
Plantier, Vanessa (Aix-Marseille University)
Sanchez Brualla, Irene (Aix-Marseille University)
Dingu, Nejada (Aix-Marseille University)
Brocard, Cécile (Aix-Marseille University)
Liabeuf, Sylvie (Aix-Marseille University)
Gackière, Florian (Aix-Marseille University)
Brocard, Frédéric (Aix-Marseille University)

Data:	2019
Resum:	Up-regulation of the persistent sodium current (INaP) and down-regulation of the potassium/chloride extruder KCC2 lead to spasticity after spinal cord injury (SCI). We here identified calpain as the driver of the up-and down-regulation of INaP and KCC2, respectively, in neonatal rat lumbar motoneurons. Few days after SCI, neonatal rats developed behavioral signs of spasticity with the emergence of both hyperreflexia and abnormal involuntary muscle contractions on hindlimbs. At the same time, in vitro isolated lumbar spinal cords became hyperreflexive and displayed numerous spontaneous motor outputs. Calpain-I expression paralleled with a proteolysis of voltage-gated sodium (Nav) channels and KCC2. Acute inhibition of calpains reduced this proteolysis, restored the motoneuronal expression of Nav and KCC2, normalized INaP and KCC2 function, and curtailed spasticity. In sum, by up-and down-regulating INaP and KCC2, the calpain-mediated proteolysis of Nav and KCC2 drives the hyperexcitability of motoneurons which leads to spasticity after SCI.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	eLife, Vol. 8 (December 2019) , p. e51404, ISSN 2050-084X

DOI: 10.7554/eLife.51404
PMID: 31815668

26 p, 3.2 MB

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