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

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

doi:10.1093/hmg/ddr335

Item

ITEM ACTIONSEXPORT

Add to Basket

Local TagsRelease HistoryDetailsSummary

Released

Journal Article

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

MPS-Authors

/persons/resource/persons38927

Klein, Rüdiger
Department: Molecular Neurobiology / Klein, MPI of Neurobiology, Max Planck Society;

External Resource

No external resources are shared

Fulltext (restricted access)

There are currently no full texts shared for your IP range.

Fulltext (public)

There are no public fulltexts stored in PuRe

Supplementary Material (public)

There is no public supplementary material available

Citation

Zhai, J., Zhou, W., Li, J., Hayworth, C. R., Zhang, L., Misawa, H., et al. (2011). The in vivo contribution of motor neuron TrkB receptors to mutant SOD1 motor neuron disease. Human Molecular Genetics, 20(21), 4116-4131. doi:10.1093/hmg/ddr335.

Cite as: https://hdl.handle.net/11858/00-001M-0000-0012-30A7-5

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.