Anterograde transport and secretion of brain-derived neurotrophic factor along sensory axons promote Schwann cell myelination.
The neurotrophin brain-derived neurotrophic factor (BDNF) inhibits Schwann cell (SC) migration and promotes myelination via the p75 neurotrophin receptor (NTR). Despite these recent findings, the expression, localization, and mechanism of BDNF action has yet to be determined. Here we demonstrate that the sensory neurons of the dorsal root ganglion (DRG) are a major source of BDNF during postnatal development. The expression of BDNF is initially elevated before myelination and decreases dramatically after the onset of myelination. BDNF expression is controlled in part by transcriptional regulation and the increased expression of the truncated TrkB receptor on SCs. To investigate the possible mechanism of BDNF transport and release, multicompartment Campenot chambers were used. DRG neurons transported and secreted endogenous BDNF along the surface of axons in anterograde fashion. In an attempt to enhance myelination by SCs, DRG neurons were transduced with an adenovirus to overexpress BDNF. BDNF was transported and secreted along the axons and enhanced myelination when compared with control cocultures. Together, the events surrounding the expression, localization, and mechanism of BDNF action in DRG neurons may hint at potential therapeutic implications to efficiently promote remyelination.
Ng
Benjamin K
BK
Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.
Chen
Lian
L
Mandemakers
Wilhelm
W
Cosgaya
José M
JM
Chan
Jonah R
JR
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001369:Axons / Q000378:metabolism*; D001692:Biological Transport; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D018920:Coculture Techniques; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D009186:Myelin Sheath / Q000502:physiology*; D009475:Neurons, Afferent / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000502:physiology*; D014018:Tissue Distribution
D019208:Brain-Derived Neurotrophic Factor