PT  - JOURNAL ARTICLE
AU  - Fletcher, Jessica L
AU  - Wood, Rhiannon J
AU  - Nguyen, Jacqueline
AU  - Norman, Eleanor ML
AU  - Jun, Christine MK
AU  - Prawdiuk, Alexa R
AU  - Biemond, Melissa
AU  - Nguyen, Huynh TH
AU  - Northfield, Susan E
AU  - Hughes, Richard A
AU  - Gonsalvez, David G
AU  - Xiao, Junhua
AU  - Murray, Simon S
TI  - Targeting TrkB with a brain-derived neurotrophic factor mimetic promotes myelin repair in the brain
AID  - 10.1101/268300
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 268300
4099  - http://biorxiv.org/content/early/2018/02/20/268300.short
4100  - http://biorxiv.org/content/early/2018/02/20/268300.full
AB  - 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. 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 pre-myelinating 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.