Supplementary Material for: Brain-Derived Neurotrophic Factor Promotes Central Nervous System Myelination via a Direct Effect upon Oligodendrocytes

The extracellular factors that are responsible for inducing myelination in the central nervous system (CNS) remain elusive. We investigated whether brain-derived neurotrophic factor (BDNF) is implicated, by first confirming that BDNF heterozygous mice exhibit delayed CNS myelination during early postnatal development. We next established that the influence of BDNF upon myelination was direct, by acting on oligodendrocytes, using co-cultures of dorsal root ganglia neurons and oligodendrocyte precursor cells. Importantly, we found that BDNF retains its capacity to enhance myelination of neurons or by oligodendrocytes derived from p75NTR knockout mice, indicating the expression of p75NTR is not necessary for BDNF-induced myelination. Conversely, we observed that phosphorylation of TrkB correlated with myelination, and that inhibiting TrkB signalling also inhibited the promyelinating effect of BDNF, suggesting that BDNF enhances CNS myelination via activating oligodendroglial TrkB-FL receptors. Together, our data reveal a previously unknown role for BDNF in potentiating the normal development of CNS myelination, via signalling within oligodendrocytes.诱导中枢神经系统（CNS）髓鞘形成的细胞外因子至今仍未明确。本研究旨在探讨脑源性神经营养因子（BDNF）是否参与该调控过程：首先证实BDNF杂合小鼠在出生后早期发育阶段，其中枢神经系统髓鞘形成存在延迟现象。随后，通过构建背根神经节神经元与少突胶质前体细胞的共培养体系，我们证明BDNF对髓鞘形成的影响具有直接性，即通过直接作用于少突胶质细胞实现。值得注意的是，我们发现BDNF仍可增强来源于p75神经营养因子受体（p75NTR）敲除小鼠的神经元或少突胶质细胞的髓鞘形成能力，这表明p75NTR的表达并非BDNF诱导髓鞘形成所必需的条件。与之相对，我们观察到酪氨酸激酶受体B（TrkB）的磷酸化水平与髓鞘形成进程密切相关，且抑制TrkB信号通路同样会阻断BDNF的促髓鞘形成作用，由此提示BDNF通过激活少突胶质细胞内的TrkB-FL受体，增强中枢神经系统的髓鞘形成。综上，本研究数据揭示了BDNF通过少突胶质细胞内的信号传导，在促进中枢神经系统髓鞘正常发育中发挥此前未被发现的关键作用。