Identification of a resilient mouse facial motoneuron population following target disconnection by injury or disease

Deborah O. Setter, Melissa M. Haulcomb, Taylor Beahrs, Rena M. Meadows, Nicole D. Schartz, Sara K. Custer, Virginia M. Sanders, Kathryn Jones

Research output: Contribution to journalArticle

Abstract

Background: When nerve transection is performed on adult rodents, a substantial population of neurons survives short-term disconnection from target, and the immune system supports this neuronal survival, however long-term survival remains unknown. Understanding the effects of permanent axotomy on cell body survival is important as target disconnection is the first pathological occurrence in fatal motoneuron diseases such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). Objective: The goal of this study was to determine if facial motoneurons (FMN) could survive permanent target disconnection up to 26 weeks post-operation (wpo) after facial nerve axotomy (FNA). In addition, the potentially additive effects of immunodeficiency and motoneuron disease on post-axotomy FMN survival were examined. Methods: This study included three wild type (WT) mouse strains (C57BL/6J, B6SJL, and FVB/NJ) and three experimental models (RAG-2 -/-: immunodeficiency; mSOD1: ALS; Smn -/- /SMN2 +/+: SMA). All animals received a unilateral FNA, and FMN survival was quantified at early and extended post-operative timepoints. Results: In the C57BL/6J WT group, FMN survival significantly decreased at 10 wpo (55±6%), and then remained stable out to 26 wpo (47±6%). In the RAG-2 -/- and mSOD1 groups, FMN death occurred much earlier at 4 wpo, and survival plateaued at approximately 50% at 10 wpo. The SMA model and other WT strains also exhibited approximately 50% FMN survival after FNA. Conclusion: These results indicate that immunodeficiency and motoneuron disease accelerate axotomy-induced neuron death, but do not increase total neuron death in the context of permanent target disconnection. This consistent finding of a target disconnection-resilient motoneuron population is prevalent in other peripheral nerve injury models and in neurodegenerative disease models as well. Characterization of the distinct populations of vulnerable and resilient motoneurons may reveal new therapeutic approaches for injury and disease.

Original languageEnglish (US)
Pages (from-to)417-422
Number of pages6
JournalRestorative Neurology and Neuroscience
Volume36
Issue number3
DOIs
StatePublished - Jan 1 2018

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Health Services Needs and Demand
Motor Neurons
Axotomy
Wounds and Injuries
Spinal Muscular Atrophy
Facial Nerve
Survival
Amyotrophic Lateral Sclerosis
Neurons
Wiskott-Aldrich Syndrome
Peripheral Nerve Injuries
Vulnerable Populations
Inbred C57BL Mouse
Neurodegenerative Diseases
Population
Immune System
Rodentia
Cell Survival
Theoretical Models

Keywords

  • amyotrophic lateral sclerosis
  • axotomy
  • Motoneuron
  • motor neuron
  • neuron survival
  • peripheral nerve injury
  • spinal muscular atrophy

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience
  • Clinical Neurology

Cite this

Identification of a resilient mouse facial motoneuron population following target disconnection by injury or disease. / Setter, Deborah O.; Haulcomb, Melissa M.; Beahrs, Taylor; Meadows, Rena M.; Schartz, Nicole D.; Custer, Sara K.; Sanders, Virginia M.; Jones, Kathryn.

In: Restorative Neurology and Neuroscience, Vol. 36, No. 3, 01.01.2018, p. 417-422.

Research output: Contribution to journalArticle

Setter, Deborah O. ; Haulcomb, Melissa M. ; Beahrs, Taylor ; Meadows, Rena M. ; Schartz, Nicole D. ; Custer, Sara K. ; Sanders, Virginia M. ; Jones, Kathryn. / Identification of a resilient mouse facial motoneuron population following target disconnection by injury or disease. In: Restorative Neurology and Neuroscience. 2018 ; Vol. 36, No. 3. pp. 417-422.
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abstract = "Background: When nerve transection is performed on adult rodents, a substantial population of neurons survives short-term disconnection from target, and the immune system supports this neuronal survival, however long-term survival remains unknown. Understanding the effects of permanent axotomy on cell body survival is important as target disconnection is the first pathological occurrence in fatal motoneuron diseases such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). Objective: The goal of this study was to determine if facial motoneurons (FMN) could survive permanent target disconnection up to 26 weeks post-operation (wpo) after facial nerve axotomy (FNA). In addition, the potentially additive effects of immunodeficiency and motoneuron disease on post-axotomy FMN survival were examined. Methods: This study included three wild type (WT) mouse strains (C57BL/6J, B6SJL, and FVB/NJ) and three experimental models (RAG-2 -/-: immunodeficiency; mSOD1: ALS; Smn -/- /SMN2 +/+: SMA). All animals received a unilateral FNA, and FMN survival was quantified at early and extended post-operative timepoints. Results: In the C57BL/6J WT group, FMN survival significantly decreased at 10 wpo (55±6{\%}), and then remained stable out to 26 wpo (47±6{\%}). In the RAG-2 -/- and mSOD1 groups, FMN death occurred much earlier at 4 wpo, and survival plateaued at approximately 50{\%} at 10 wpo. The SMA model and other WT strains also exhibited approximately 50{\%} FMN survival after FNA. Conclusion: These results indicate that immunodeficiency and motoneuron disease accelerate axotomy-induced neuron death, but do not increase total neuron death in the context of permanent target disconnection. This consistent finding of a target disconnection-resilient motoneuron population is prevalent in other peripheral nerve injury models and in neurodegenerative disease models as well. Characterization of the distinct populations of vulnerable and resilient motoneurons may reveal new therapeutic approaches for injury and disease.",
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AU - Haulcomb, Melissa M.

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AU - Meadows, Rena M.

AU - Schartz, Nicole D.

AU - Custer, Sara K.

AU - Sanders, Virginia M.

AU - Jones, Kathryn

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N2 - Background: When nerve transection is performed on adult rodents, a substantial population of neurons survives short-term disconnection from target, and the immune system supports this neuronal survival, however long-term survival remains unknown. Understanding the effects of permanent axotomy on cell body survival is important as target disconnection is the first pathological occurrence in fatal motoneuron diseases such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). Objective: The goal of this study was to determine if facial motoneurons (FMN) could survive permanent target disconnection up to 26 weeks post-operation (wpo) after facial nerve axotomy (FNA). In addition, the potentially additive effects of immunodeficiency and motoneuron disease on post-axotomy FMN survival were examined. Methods: This study included three wild type (WT) mouse strains (C57BL/6J, B6SJL, and FVB/NJ) and three experimental models (RAG-2 -/-: immunodeficiency; mSOD1: ALS; Smn -/- /SMN2 +/+: SMA). All animals received a unilateral FNA, and FMN survival was quantified at early and extended post-operative timepoints. Results: In the C57BL/6J WT group, FMN survival significantly decreased at 10 wpo (55±6%), and then remained stable out to 26 wpo (47±6%). In the RAG-2 -/- and mSOD1 groups, FMN death occurred much earlier at 4 wpo, and survival plateaued at approximately 50% at 10 wpo. The SMA model and other WT strains also exhibited approximately 50% FMN survival after FNA. Conclusion: These results indicate that immunodeficiency and motoneuron disease accelerate axotomy-induced neuron death, but do not increase total neuron death in the context of permanent target disconnection. This consistent finding of a target disconnection-resilient motoneuron population is prevalent in other peripheral nerve injury models and in neurodegenerative disease models as well. Characterization of the distinct populations of vulnerable and resilient motoneurons may reveal new therapeutic approaches for injury and disease.

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