Motoneuron programmed cell death in response to proBDNF

Dev Neurobiol. 2012 May;72(5):699-712. doi: 10.1002/dneu.20964.

Abstract

Motoneurons (MN) as well as most neuronal populations undergo a temporally and spatially specific period of programmed cell death (PCD). Several factors have been considered to regulate the survival of MNs during this period, including availability of muscle-derived trophic support and activity. The possibility that target-derived factors may also negatively regulate MN survival has been considered, but not pursued. Neurotrophin precursors, through their interaction with p75(NTR) and sortilin receptors have been shown to induce cell death during development and following injury in the CNS. In this study, we find that muscle cells produce and secrete proBDNF. ProBDNF through its interaction with p75(NTR) and sortilin, promotes a caspase-dependent death of MNs in culture. We also provide data to suggest that proBDNF regulates MN PCD during development in vivo.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Vesicular Transport / antagonists & inhibitors
  • Adaptor Proteins, Vesicular Transport / metabolism
  • Animals
  • Apoptosis / physiology*
  • Astrocytes / cytology
  • Brain-Derived Neurotrophic Factor / antagonists & inhibitors
  • Brain-Derived Neurotrophic Factor / biosynthesis
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Caspase 3 / metabolism
  • Caspase 7 / metabolism
  • Cell Communication / physiology
  • Chick Embryo
  • Chickens
  • Gene Expression Regulation, Developmental / physiology
  • Motor Neurons / metabolism*
  • Muscle Fibers, Skeletal / cytology
  • Muscle Fibers, Skeletal / metabolism
  • Muscle, Skeletal / embryology*
  • Muscle, Skeletal / innervation
  • Muscle, Skeletal / metabolism
  • Primary Cell Culture
  • Protein Precursors / antagonists & inhibitors
  • Protein Precursors / metabolism*
  • Receptor, Nerve Growth Factor / metabolism
  • Spinal Cord / cytology
  • Spinal Cord / embryology*

Substances

  • Adaptor Proteins, Vesicular Transport
  • Brain-Derived Neurotrophic Factor
  • Protein Precursors
  • Receptor, Nerve Growth Factor
  • brain-derived neurotrophic factor precursor
  • Caspase 3
  • Caspase 7
  • sortilin