Neurodegenerative changes are prevented by Erythropoietin in the pmn model of motoneuron degeneration.
Motoneuron diseases are fatal neurodegenerative disorders characterized by a progressive loss of motoneurons, muscle weakness and premature death. The progressive motor neuronopathy (pmn) mutant mouse has been considered a good model for the autosomal recessive childhood form of spinal muscular atrophy (SMA). Here, we investigated the therapeutic potential of Erythropoietin (Epo) on this mutant mouse. Symptomatic or pre-symptomatic treatment with Epo significantly prolongs lifespan by 84.6% or 87.2% respectively. Epo preserves muscle strength and significantly attenuates behavioural motor deficits of mutant pmn mice. Histological and metabolic changes in the spinal cord evaluated by immunohistochemistry, western blot, and high-resolution (1)H-NMR spectroscopy were also greatly prevented by Epo-treatment. Our results illustrate the efficacy of Epo in improving quality of life of mutant pmn mice and open novel therapeutic pathways for motoneuron diseases.
Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas (CSIC) - Universidad Miguel Hernández (UMH), Av. Ramón y Cajal s/n, 03550 San Juan de Alicante, Alicante, Spain.
Marta
M
Ruiz
Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas (CSIC) - Universidad Miguel Hernández (UMH), Av. Ramón y Cajal s/n, 03550 San Juan de Alicante, Alicante, Spain.
Ana Fe
AF
Martínez-Vidal
Unidad Central de Investigación en Medicina, Universidad de Valencia, Valencia, Spain.
José Manuel
JM
Morales
Fundación de Investigación del Hospital Clínico Universitario de Valencia (FIHCUV), Valencia, Spain.
Daniel
D
Monleón
Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas (CSIC) - Universidad Miguel Hernández (UMH), Av. Ramón y Cajal s/n, 03550 San Juan de Alicante, Alicante, Spain. Electronic address: minergyr@gmail.com.
Minerva
M
Giménez Y Ribotta
D000818:Animals; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000627:therapeutic use*; D051379:Mice; D008817:Mice, Mutant Strains; D009043:Motor Activity / Q000187:drug effects; D009046:Motor Neurons / Q000187:drug effects*; D017467:Receptors, Erythropoietin / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D014897:Spinal Muscular Atrophies of Childhood / Q000188:drug therapy*
D017467:Receptors, Erythropoietin; D004921:Erythropoietin
Erythropoietin; Motoneuron diseases; Proton NMR spectroscopy ex vivo; Spinal muscular atrophy; pmn mutant mouse