Neurodegenerative changes are prevented by Erythropoietin in the pmn model of motoneuron degeneration

•Epo prolongs lifespan, and preserves weight, muscle strength and behaviour of mice.•Epo preserves cis-Golgi proteins and prevents Golgi fragmentation in motoneurons.•Epo preserves pattern of descending afferents and their modulating action on targets.•Epo prevents astroglial reaction and facilitates astrocytic homeostasis.•Epo maintains key metabolite levels determined by 1H-NMR spectroscopy.

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.

Graphical abstractBody 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 < 0.05, **p < 0.01 (two way ANOVA followed by the Bonferroni post-hoc test)Figure optionsDownload full-size imageDownload as PowerPoint slide