Brain-Derived Neurotrophic Factor (BDNF) plays important roles in promoting myelination in the developing central nervous system (CNS), however the influence it exerts on oligodendrocyte development in vivo remains unclear. As BDNF knockout mice die in the perinatal period, we undertook a systematic developmental analysis of oligodendroglial lineage cells within multiple CNS regions of BDNF heterozygous (HET) mice. Our data identify that BDNF heterozygosity results in transient reductions in oligodendroglial lineage cell density and progression that are largely restricted to the optic nerve, whereas the corpus callosum, cerebral cortex, basal forebrain and spinal cord white matter tracts are unaffected. In the first two postnatal weeks, BDNF HET mice exhibit reductions in the density of oligodendroglial lineage cells, oligodendrocyte precursor cells (OPCs) and postmitotic oligodendrocytes selectively in the optic nerve, but not in the brain or spinal cord white matter tracts. However, this normalizes later in development. The overall proportion of OPCs and mature oligodendrocytes remains unchanged from P9 to P30 in all CNS regions. This study identifies that BDNF exerts transient effects on oligodendroglial lineage cells selectively in the optic nerve during postnatal development. Taken together, this provides compelling evidence that BDNF haploinsufficiency exerts modest effects upon oligodendroglial cell density and lineage progression in vivo, suggesting its major role is restricted to promoting oligodendrocyte myelination.

脑源性神经营养因子（BDNF）在促进中枢神经系统（CNS）发育中的髓鞘形成中发挥重要作用，但其对体内少突胶质细胞发育的影响仍不清楚。由于 BDNF 敲除小鼠在围产期死亡，我们对 BDNF 杂合子 (HET) 小鼠多个 CNS 区域内的少突胶质细胞谱系细胞进行了系统的发育分析。我们的数据表明，BDNF 杂合性导致少突胶质细胞谱系细胞密度和进展的短暂减少，这主要限于视神经，而胼胝体、大脑皮层、基底前脑和脊髓白质束不受影响。在出生后的前两周，BDNF HET 小鼠在视神经中选择性地表现出少突胶质细胞谱系细胞、少突胶质细胞前体细胞 (OPC) 和有丝分裂后少突胶质细胞的密度降低，但在大脑或脊髓白质束中则没有。然而，这在开发后期会正常化。在所有 CNS 区域中，从 P9 到 P30，OPC 和成熟少突胶质细胞的总体比例保持不变。这项研究发现，BDNF 在出生后发育过程中选择性地对视神经中的少突胶质细胞谱系细胞产生短暂影响。总而言之，这提供了令人信服的证据，表明 BDNF 单倍体不足对体内少突胶质细胞密度和谱系进展产生适度影响，表明其主要作用仅限于促进少突胶质细胞髓鞘形成。