Translatomic analysis of regenerating and degenerating spinal motor neurons in injury and ALS
Jennifer L. Shadrach,
Wesley M. Stansberry,
Allison M. Milen,
Rachel E. Ives,
Elizabeth A. Fogarty,
Anthony Antonellis,
Brian A. Pierchala
Affiliations
Jennifer L. Shadrach
Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI, USA; Cellular and Molecular Biology Graduate Program, University of Michigan, Ann Arbor, MI, USA
Wesley M. Stansberry
Department of Anatomy, Cell Biology & Physiology, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA
Allison M. Milen
Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI, USA
Rachel E. Ives
Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI, USA
Elizabeth A. Fogarty
Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA
Anthony Antonellis
Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI, USA; Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA; Department of Neurology, University of Michigan, Ann Arbor, MI, USA
Brian A. Pierchala
Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI, USA; Cellular and Molecular Biology Graduate Program, University of Michigan, Ann Arbor, MI, USA; Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI, USA; Department of Anatomy, Cell Biology & Physiology, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA; Corresponding author
Summary: 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 SOD1G93A ALS model. Of the 267 transcripts upregulated after nerve crush, 38% were also upregulated in SOD1G93A 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.
