BDNF Exerts Contrasting Effects on Peripheral Myelination of NGF-Dependent and BDNF-Dependent DRG Neurons

Abstract

Although brain-derived neurotrophic factor (BDNF) has been shown to promote peripheral myelination during development and remyelination after injury, the precise mechanisms mediating this effect remain unknown. Here, we determine that BDNF promotes myelination of nerve growth factor-dependent neurons, an effect dependent on neuronal expression of the p75 neurotrophin receptor, whereas BDNF inhibits myelination of BDNF-dependent neurons via the full-length TrkB receptor. Thus, BDNF exerts contrasting effects on Schwann cell myelination, depending on the complement of BDNF receptors that are expressed by different subpopulations of dorsal root ganglion neurons. These results demonstrate that BDNF exerts contrasting modulatory roles in peripheral nervous system myelination, and that its mechanism of action is acutely regulated and specifically targeted to neurons.

Brain-derived Neurotrophic Factor (BDNF) Induces Polarized Signaling of Small GTPase (Rac1) Protein at the Onset of Schwann Cell Myelination through Partitioning-defective 3 (Par3) Protein

“…A recent study by Xiao et al (27) demonstrated that BDNF promoted myelination through p75 from the neuron side and MO1 reduces Pard3 protein levels and inhibits RacGTP levels in zebrafish larvae. Embryos at 4 dpf were deyolked, and proteins were extracted for RacGTP assays and control Western blot analyses.…”

Nanotechnology versus stem cell engineering: in vitro comparison of neurite inductive potentials

“…DRG neuron populations are heterogeneous with regard to the quality of sensory transmission, and different growth factors act selectively on different subpopulations of DRG neurons. [26][27][28][29] Therefore, an emerging concept in the field of artificial nerve graft development is to use a combination of NTFs with the aim to obtain a widespread effect on all sensory, motor, and sympathetic neuronal subpopulations. [30][31][32] It is, however, still under debate which NTF combination will result in the most successful support of PNR while simultaneously avoiding negative influences in the process.…”

Production and Use of Lentivirus to Selectively Transduce Primary Oligodendrocyte Precursor Cells for <em>In Vitro</em> Myelination Assays

“…Prior to the OPC seeding, completely aspirate media from the DRG culture plate. Gently seed 200,000 OPCs drop wise on to the DRG neurons as previously described [4][5][6] . NOTE: The total OPC seeding volume must be less than 200 µl per 22 mm coverslip.…”

“…8. Assess the co-cultures for myelin protein expression by western blot analysis and visualize for the formation of myelinated axonal segments by double-immunostaining with antibodies against myelin basic protein markers and neuronal markers [4][5][6] .…”

“…Specialized cells, Schwann cells in the peripheral nervous system and oligodendrocytes in the central nervous system, wrap around and ensheathe axons in myelin, effectively insulating the nerve and facilitating saltatory conduction 1 . The process of myelination can be studied in vitro using retinal ganglion neurons 2 , engineered nanofibers 3 , or dorsal root ganglion neurons co-cultured with either Schwann cells 4 or oligodendrocytes [5][6][7] . The in vitro myelination assay is an established model for studying nervous system myelination and it replicates many of the fundamental processes that occur during myelination in vivo [5][6][7][8] .…”