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 atro...

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Bibliographic Details
Published in:Neuropharmacology 2014-08, Vol.83, p.137-153
Main Authors: Ruiz, Marta, Martínez-Vidal, Ana Fe, Morales, José Manuel, Monleón, Daniel, Giménez y Ribotta, Minerva
Format: Article
Language:English
Subjects:
Animals
Disease Models, Animal
Erythropoietin
Erythropoietin - therapeutic use
Mice
Mice, Mutant Strains
Motoneuron diseases
Motor Activity - drug effects
Motor Neurons - drug effects
pmn mutant mouse
Proton NMR spectroscopy ex vivo
Receptors, Erythropoietin - metabolism
Spinal Cord - drug effects
Spinal Cord - metabolism
Spinal Muscular Atrophies of Childhood - drug therapy
Spinal muscular atrophy
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Summary: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 1H-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. Body weight evolution. All animals reached a maximal weight ─about of 10 g─ at 13 days. Then, because of the disease a progressive weight loss occurs. Afterwards, from day 17 onwards, Epo1 and Epo2-treated mice maintained significantly their body weight unlike untreated pmn mutant mice, even a long time after animals received the last dose of Epo. This represents a body weight increase of 36.2% and of 44.8% respectively. *p 
ISSN:0028-3908
1873-7064
DOI:10.1016/j.neuropharm.2014.04.009