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

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 later...

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Main Authors: Jennifer L. Shadrach, Wesley M. Stansberry, Allison M. Milen, Rachel E. Ives, Elizabeth A. Fogarty, Anthony Antonellis, Brian A. Pierchala
Format: Article
Language:English
Published: Elsevier 2021-07-01
Series:iScience
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004221006684
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author Jennifer L. Shadrach
Wesley M. Stansberry
Allison M. Milen
Rachel E. Ives
Elizabeth A. Fogarty
Anthony Antonellis
Brian A. Pierchala
author_facet Jennifer L. Shadrach
Wesley M. Stansberry
Allison M. Milen
Rachel E. Ives
Elizabeth A. Fogarty
Anthony Antonellis
Brian A. Pierchala
author_sort Jennifer L. Shadrach
collection DOAJ
description 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.
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spelling doaj.art-9b219a5bad5347d8bcd6aa7790a2e9152022-12-21T18:51:18ZengElsevieriScience2589-00422021-07-01247102700Translatomic analysis of regenerating and degenerating spinal motor neurons in injury and ALSJennifer L. Shadrach0Wesley M. Stansberry1Allison M. Milen2Rachel E. Ives3Elizabeth A. Fogarty4Anthony Antonellis5Brian A. Pierchala6Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI, USA; Cellular and Molecular Biology Graduate Program, University of Michigan, Ann Arbor, MI, USADepartment of Anatomy, Cell Biology & Physiology, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USADepartment of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI, USADepartment of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI, USADepartment of Human Genetics, University of Michigan, Ann Arbor, MI, USANeuroscience 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, USADepartment 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 authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004221006684Biological sciencesNeuroscienceSensory neuroscienceTechniques in neuroscience
spellingShingle Jennifer L. Shadrach
Wesley M. Stansberry
Allison M. Milen
Rachel E. Ives
Elizabeth A. Fogarty
Anthony Antonellis
Brian A. Pierchala
Translatomic analysis of regenerating and degenerating spinal motor neurons in injury and ALS
iScience
Biological sciences
Neuroscience
Sensory neuroscience
Techniques in neuroscience
title Translatomic analysis of regenerating and degenerating spinal motor neurons in injury and ALS
title_full Translatomic analysis of regenerating and degenerating spinal motor neurons in injury and ALS
title_fullStr Translatomic analysis of regenerating and degenerating spinal motor neurons in injury and ALS
title_full_unstemmed Translatomic analysis of regenerating and degenerating spinal motor neurons in injury and ALS
title_short Translatomic analysis of regenerating and degenerating spinal motor neurons in injury and ALS
title_sort translatomic analysis of regenerating and degenerating spinal motor neurons in injury and als
topic Biological sciences
Neuroscience
Sensory neuroscience
Techniques in neuroscience
url http://www.sciencedirect.com/science/article/pii/S2589004221006684
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