The in vivo contribution of motor neuron TrkB receptors to mutant SOD1 motor neuron disease

Jinbin Zhai, Weiguo Zhou, Jian Li, Christopher R. Hayworth, Lei Zhang, Hidemi Misawa, Rudiger Klein, Steven S. Scherer, Rita J. Balice-Gordon, Robert Gordon Kalb

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin-related kinase B (TrkB) are widely expressed in the vertebrate nervous system and play a central role in mature neuronal function. In vitro BDNF/TrkB signaling promotes neuronal survival and can help neurons resist toxic insults. Paradoxically, BDNF/TrkB signaling has also been shown, under certain in vitro circumstances, to render neurons vulnerable to insults. We show here that in vivo conditional deletion of TrkB from mature motor neurons attenuates mutant superoxide dismutase 1 (SOD1) toxicity. Mutant SOD1 mice lacking motor neuron TrkB live a month longer than controls and retain motor function for a longer period, particularly in the early phase of the disease. These effects are subserved by slowed motor neuron loss, persistence of neuromuscular junction integrity and reduced astrocytic and microglial reactivity within the spinal cord. These results suggest that manipulation of BDNF/TrkB signaling might have therapeutic efficacy in motor neuron diseases.

Original languageEnglish
Article numberddr335
Pages (from-to)4116-4131
Number of pages16
JournalHuman molecular genetics
Volume20
Issue number21
DOIs
Publication statusPublished - 2011 Nov 1

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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    Zhai, J., Zhou, W., Li, J., Hayworth, C. R., Zhang, L., Misawa, H., Klein, R., Scherer, S. S., Balice-Gordon, R. J., & Kalb, R. G. (2011). The in vivo contribution of motor neuron TrkB receptors to mutant SOD1 motor neuron disease. Human molecular genetics, 20(21), 4116-4131. [ddr335]. https://doi.org/10.1093/hmg/ddr335