BDNF overexpression produces a long-term increase in myelin formation in the peripheral nervous system.
The neurotrophin brain-derived neurotrophic factor (BDNF) is an endogenous regulator of the myelination process during development in the peripheral nervous system. Enhancement of myelin formation by BDNF is mediated by the neurotrophin receptor p75(NTR). Although this neurotrophin is a positive modulator of myelination during early development, the final effects of BDNF on myelin sheaths after active myelination is completed are largely unknown. Using BDNF transgenic mice, we examined the long-term effects of BDNF on myelination of the peripheral nervous system in vivo. Elevation of BDNF levels in the transgenic mice produced an increase in both the rate and extent of the myelination process. BDNF enhanced and accelerated myelin formation during early development and this increase in myelin content and thickness was maintained in adulthood. Besides enhanced myelination, BDNF also influenced axon caliber size but to a lesser extent. This lagging increase in axon caliber compared to myelin suggests that the axon size is not the only determinant of myelin thickness.
Tolwani
Ravi J
RJ
Department of Comparative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA. rtolwani@stanford.edu.
Cosgaya
José M
JM
Varma
Sushama
S
Jacob
Reza
R
Kuo
Lydia E
LE
Shooter
Eric M
EM
D000818:Animals; D001369:Axons / Q000648:ultrastructure; D015139:Blotting, Southern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009185:Myelin Proteins / Q000378:metabolism*; D009186:Myelin Sheath / Q000502:physiology*; D017933:Peripheral Nervous System / Q000502:physiology* / Q000648:ultrastructure; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012584:Sciatic Nerve / Q000378:metabolism / Q000648:ultrastructure; D013997:Time Factors
D019208:Brain-Derived Neurotrophic Factor; D009185:Myelin Proteins; D012333:RNA, Messenger