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Sarm1 is not necessary for activation of neuron-intrinsic growth programs yet required for the Schwann cell repair response and peripheral nerve regeneration.
Schmitd, Ligia B; Hafner, Hannah; Ward, Ayobami; Asghari Adib, Elham; Biscola, Natalia P; Kohen, Rafi; Patel, Manav; Williamson, Rachel E; Desai, Emily; Bennett, Julianna; Saxman, Grace; Athaiya, Mitre; Wilborn, David; Shumpert, Jaisha; Zhao, Xiao-Feng; Kawaguchi, Riki; Geschwind, Daniel H; Hoke, Ahmet; Shrager, Peter; Collins, Catherine A; Havton, Leif A; Kalinski, Ashley L; Giger, Roman J.
Afiliación
  • Schmitd LB; Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor MI, USA.
  • Hafner H; Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor MI, USA.
  • Ward A; Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor MI, USA.
  • Asghari Adib E; Department of Neurosurgery, University of Michigan Medical School, Ann Arbor MI, USA.
  • Biscola NP; Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, USA.
  • Kohen R; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Patel M; Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor MI, USA.
  • Williamson RE; Department of Biology, Ball State University, Muncie IN, USA.
  • Desai E; Department of Biology, Ball State University, Muncie IN, USA.
  • Bennett J; Department of Biology, Ball State University, Muncie IN, USA.
  • Saxman G; Department of Biology, Ball State University, Muncie IN, USA.
  • Athaiya M; Department of Biology, Ball State University, Muncie IN, USA.
  • Wilborn D; Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor MI, USA.
  • Shumpert J; Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor MI, USA.
  • Zhao XF; Department of Biology, Ball State University, Muncie IN, USA.
  • Kawaguchi R; Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor MI, USA.
  • Geschwind DH; Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
  • Hoke A; Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
  • Shrager P; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
  • Collins CA; Institute of Precision Health, University of California, Los Angeles, Los Angeles, CA, USA.
  • Havton LA; Department of Neurology, The Johns Hopkins University, Baltimore, MD, USA.
  • Kalinski AL; Department of Neuroscience, University of Rochester Medical Center, Rochester, NY, USA.
  • Giger RJ; Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, USA.
bioRxiv ; 2024 Apr 17.
Article en En | MEDLINE | ID: mdl-38496662
ABSTRACT
Upon peripheral nervous system (PNS) injury, severed axons undergo rapid SARM1-dependent Wallerian degeneration (WD). In mammals, the role of SARM1 in PNS regeneration, however, is unknown. Here we demonstrate that Sarm1 is not required for axotomy induced activation of neuron-intrinsic growth programs and axonal growth into a nerve crush site. However, in the distal nerve, Sarm1 is necessary for the timely induction of the Schwann cell (SC) repair response, nerve inflammation, myelin clearance, and regeneration of sensory and motor axons. In Sarm1-/- mice, regenerated fibers exhibit reduced axon caliber, defective nerve conduction, and recovery of motor function is delayed. The growth hostile environment of Sarm1-/- distal nerve tissue was demonstrated by grafting of Sarm1-/- nerve into WT recipients. SC lineage tracing in injured WT and Sarm1-/- mice revealed morphological differences. In the Sarm1-/- distal nerve, the appearance of p75NTR+, c-Jun+ SCs is significantly delayed. Ex vivo, p75NTR and c-Jun upregulation in Sarm1-/- nerves can be rescued by pharmacological inhibition of ErbB kinase. Together, our studies show that Sarm1 is not necessary for the activation of neuron intrinsic growth programs but in the distal nerve is required for the orchestration of cellular programs that underlie rapid axon extension.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos