Negative regulation by proBDNF signaling of peripheral neurogenesis in the sensory ganglia of adult rats

Biomed Pharmacother. 2021 Dec:144:112273. doi: 10.1016/j.biopha.2021.112273. Epub 2021 Oct 23.

Abstract

Neurogenesis in the adult brain is well recognized and plays a critical role in the maintenance of brain function and homeostasis. However, whether neurogenesis also occurs in the adult peripheral nervous system remains unknown. Here, using sensory ganglia (dorsal root ganglia, DRGs) as a model, we show that neurogenesis also occurs in the peripheral nervous system, but in a manner different from that in the central nervous system. Satellite glial cells (SGCs) express the neuronal precursor markers Nestin, POU domain, class 4, transcription factor 1, and p75 pan-neurotrophin receptor. Following sciatic nerve injury, the suppression of endogenous proBDNF by proBDNF antibodies resulted in the transformation of proliferating SGCs into doublecortin-positive cells in the DRGs. Using purified SGCs migrating out from the DRGs, the inhibition of endogenous proBDNF promoted the conversion of SGCs into neuronal phenotypes in vitro. Our findings suggest that SGCs are neuronal precursors, and that proBDNF maintains the SGC phenotype. Furthermore, the suppression of proBDNF signaling is necessary for neuronal phenotype acquisition by SGCs. Thus, we propose that peripheral neurogenesis may occur via the direct conversion of SGCs into neurons, and that this process is negatively regulated by proBDNF.

Keywords: DRG-SGCs; Neuronal precursor cells; ProBDNF; Sciatic nerve injury; Transdifferentiation.

MeSH terms

  • Action Potentials
  • Animals
  • Animals, Newborn
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Cell Transdifferentiation
  • Cells, Cultured
  • Disease Models, Animal
  • Doublecortin Protein / metabolism
  • Female
  • Ganglia, Spinal / metabolism*
  • Ganglia, Spinal / pathology
  • Ganglia, Spinal / physiopathology
  • Male
  • Neural Stem Cells / metabolism*
  • Neural Stem Cells / pathology
  • Neurogenesis*
  • Neuroglia / metabolism*
  • Neuroglia / pathology
  • Peripheral Nerve Injuries / metabolism*
  • Peripheral Nerve Injuries / pathology
  • Peripheral Nerve Injuries / physiopathology
  • Phenotype
  • Protein Precursors / genetics
  • Protein Precursors / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Nerve Growth Factor / genetics
  • Receptors, Nerve Growth Factor / metabolism
  • Signal Transduction

Substances

  • Bdnf protein, rat
  • Brain-Derived Neurotrophic Factor
  • Dcx protein, rat
  • Doublecortin Protein
  • Protein Precursors
  • Receptors, Nerve Growth Factor
  • brain-derived neurotrophic factor precursor