RT Journal Article
SR Electronic
T1 Targeting TrkB with a brain-derived neurotrophic factor mimetic promotes myelin repair in the brain
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 268300
DO 10.1101/268300
A1 Fletcher, Jessica L
A1 Wood, Rhiannon J
A1 Nguyen, Jacqueline
A1 Norman, Eleanor ML
A1 Jun, Christine MK
A1 Prawdiuk, Alexa R
A1 Biemond, Melissa
A1 Nguyen, Huynh TH
A1 Northfield, Susan E
A1 Hughes, Richard A
A1 Gonsalvez, David G
A1 Xiao, Junhua
A1 Murray, Simon S
YR 2018
UL http://biorxiv.org/content/early/2018/02/20/268300.abstract
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.