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.

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