Journal article

Targeting TrkB with a Brain-Derived Neurotrophic Factor Mimetic Promotes Myelin Repair in the Brain

Jessica L Fletcher, Rhiannon J Wood, Jacqueline Nguyen, Eleanor ML Norman, Christine MK Jun, Alexa R Prawdiuk, Melissa Biemond, Huynh TH Nguyen, Susan E Northfield, Richard A Hughes, David G Gonsalvez, Junhua Xiao, Simon S Murray



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 wi..

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Awarded by Australian National Health and Medical Research Council (NHMRC) Project Grants

Awarded by Multiple Sclerosis Research Australia (MSRA) Project Grant

Awarded by MSRA Postdoctoral Fellowship

Awarded by MSRA/NHMRC Early Career Fellowship

Funding Acknowledgements

This work was supported by Australian National Health and Medical Research Council (NHMRC) Project Grants (APP1058647 to J.X. and APP1105108 to S.S.M.), a Multiple Sclerosis Research Australia (MSRA) Project Grant (13-039; S.S.M. and J.X.), a MSRA Postdoctoral Fellowship (14-056 to J.L.F.), and a MSRA/NHMRC Early Career Fellowship (APP111041 to D.G.G.). We thank Cameron Nowell (Monash University) and Dr. Verena Wimmer (The Florey Institute) for advice on image analysis procedures and automation. Confocal imaging was performed at the Biological Optical Microscope Platform, The University of Melbourne, and the Florey Advanced Microscopy and Immunohistochemistry Service, The Florey Institute of Mental Health and Neuroscience, and Peter MacCallum Centre for Advanced Histology and Microscopy f assistance with EM processing and imaging.