The levels of brain-derived neurotrophic factor (BDNF) in the corpus callosum have previously been shown to have a critical impact on oligodendrocyte (OLG) lineage cells during cuprizone-elicited demyelination. In particular, BDNF+/– mice exhibit greater losses in myelin protein levels compared to wild-type mice after cuprizone. To investigate whether OLGs may directly mediate these effects of BDNF during a lesion in vivo, we used the cuprizone model of demyelination with inducible conditional male knockout mice to specifically delete the high-affinity tropomyosin receptor kinase B (TrkB) receptor from proteolipid protein + OLGs during cuprizone-elicited demyelination and subsequent remyelination. The loss of TrkB during cuprizone-elicited demyelination results in an increased sensitivity to demyelination as demonstrated by greater deficits in myelin protein levels, greater decreases in numbers of mature OLGs, increased numbers of demyelinated axons, and decreased myelin thickness. When mice are removed from cuprizone, they exhibit a delayed recovery in myelin proteins and myelin. Our data indicate that following a demyelinating lesion, TrkB in OLGs positively regulates myelin protein expression, myelin itself, and remyelination.

胼胝体中脑源性神经营养因子 (BDNF) 的水平先前已被证明在铜宗引发的脱髓鞘过程中对少突胶质细胞 (OLG) 谱系细胞具有重要影响。特别是，与服用铜宗后的野生型小鼠相比，BDNF+/- 小鼠的髓鞘蛋白水平损失更大。研究 OLG 是否可以在体内损伤期间直接介导 BDNF 的这些作用，我们使用 cuprizone 脱髓鞘模型和可诱导条件性雄性基因敲除小鼠，在 cuprizone 引起的脱髓鞘作用和随后的髓鞘再生过程中，特异性地从蛋白脂质蛋白 + OLGs 中删除高亲和力原肌球蛋白受体激酶 B (TrkB) 受体。在 cuprizone 引起的脱髓鞘过程中 TrkB 的丢失导致对脱髓鞘的敏感性增加，表现为髓鞘蛋白水平的更大缺陷、成熟 OLG 数量的更大减少、脱髓鞘轴突数量的增加和髓鞘厚度的减少。当小鼠从 cuprizone 中取出时，它们表现出髓鞘蛋白和髓磷脂的延迟恢复。我们的数据表明，在发生脱髓鞘病变后，OLG 中的 TrkB 正向调节髓鞘蛋白表达、髓鞘本身和髓鞘再生。