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- Title
Targeting TrkB with a Brain-Derived Neurotrophic Factor Mimetic Promotes Myelin Repair in the Brain.
- Authors
Fletcher, Jessica L.; Wood, Rhiannon J.; Nguyen, Jacqueline; Norman, Eleanor M. L.; Jun, Christine M. K.; Prawdiuk, Alexa R.; Biemond, Melissa; Nguyen, Huynh T. H.; Northfield, Susan E.; Hughes, Richard A.; Gonsalvez, David G.; Junhua Xiao; Murray, Simon S.
- Abstract
Methods to promote myelin regeneration in response to central myelin loss are essential to prevent the progression of clinical disability in demyelinating diseases. The neurotrophin brain-derived neurotrophic factor (BDNF) is known to promote myelination during development via oligodendrocyte expressed TrkB receptors. Here, we use a structural mimetic of BDNF to promote myelin regeneration in a preclinical mouse model of central demyelination. In female mice, we show that selective targeting of TrkB with the BDNF-mimetic enhances remyelination, increasing oligodendrocyte differentiation, the frequency of myelinated axons, and myelin sheath thickness after a demyelinating insult. Treatment with exogenous BDNF exerted an attenuated effect, increasing myelin sheath thickness only. Further, following conditional deletion of TrkB from premyelinating oligodendrocytes, we show the effects of the BDNF-mimetic on oligodendrocyte differentiation and remyelination are lost, indicating these are dependent on oligodendrocyte expression of TrkB. Overall, these studies demonstrate that targeting oligodendrocyte TrkB promotes in vivo remyelination in the brain.
- Subjects
MYELIN; NEUROTROPHINS; MYELINATION; OLIGODENDROGLIA; AXONS
- Publication
Journal of Neuroscience, 2018, Vol 38, Issue 32, p7088
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.0487-18.2018