Translatomic analysis of regenerating and degenerating spinal motor neurons in injury and ALS

The neuromuscular junction is a synapse critical for muscle strength and coordinated motor function. Unlike CNS injuries, motor neurons mount robust regenerative responses after peripheral nerve injuries. Conversely, motor neurons selectively degenerate in diseases such as amyotrophic lateral sclerosis (ALS). To assess how these insults affect motor neurons in vivo, we performed ribosomal profiling of mouse motor neurons. Motor neuron-specific transcripts were isolated from spinal cords following sciatic nerve crush, a model of acute injury and regeneration, and in the SOD1(G93A) ALS model. Of the 267 transcripts upregulated after nerve crush, 38% were also upregulated in SOD1(G93A) motor neurons. However, most upregulated genes in injured and ALS motor neurons were context specific. Some of the most significantly upregulated transcripts in both paradigms were chemokines such as Ccl2 and Ccl7, suggesting an important role for neuroimmune modulation. Collectively these data will aid in defining pro-regenerative and pro-degenerative mechanisms in motor neurons.

Automated summary

After peripheral nerve injuries, motor neurons mount robust regenerative responses, while they selectively degenerate in diseases like ALS. Studies have shown that the upregulation of certain genes in nerve injury and ALS models is context specific, with chemokines potentially playing an important role in motor neurons.