Department of Neurosurgery, Juntendo University School of Medicine, Tokyo, Japan.
Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
Neuroscience. 2019 May 15;406:167-175. doi: 10.1016/j.neuroscience.2019.03.004. Epub 2019 Mar 10.
Oligodendrocytes (OLGs) differentiate from oligodendrocyte-precursor-cells (OPCs) for myelination in white matter. This differentiation is maintained by cell-cell interactions through trophic factors such as brain-derived-neurotrophic-factor (BDNF). However, differentiation is impaired when white matter injury occurs in a chronic cerebral hypoperfusion model. Thus, we examined the effects of the interaction between astrocyte and oligodendrocyte lineage cells on myelination regarding the mechanism of impairment. A microcoil was applied to the bilateral common carotid arteries in male C57BL/6 mice as an in vivo cerebral chronic hypoperfusion model (BCAS model). A nonlethal concentration of CoCl2 was added to the primary cell culture from the postnatal rat cortex and incubated in vitro. White matter injury progressed in the BCAS model as myelin decreased. The numbers of OPCs and astrocytes increased after the operation, whereas that of OLGs decreased at day 28. BDNF continuously decreased until day 28. Differentiation was disrupted under the stressed conditions in the cell culture, but improved after administration of astrocyte-conditioned medium containing BDNF. Astrocytes with BDNF underwent differentiation, but differentiation was impaired under the stressed conditions due to the reduction of BDNF. We examined S100B regarding the mechanism of impairment. S100B is mainly expressed by mature astrocytes, and has neuroprotective and neurotoxic effects inside and outside of cells. GFAP-positive astrocytes increased in the corpus callosum in the BCAS model, whereas the number of mature astrocytes continued to decrease, resulting in reduced BDNF. The reduction in mature astrocytes due to the discharge of S100B in ischemic conditions caused the reduction in BDNF.
少突胶质细胞（OLGs）从少突胶质前体细胞（OPCs）分化而来，以在白质中进行髓鞘形成。这种分化通过神经营养因子如脑源性神经营养因子（BDNF）等细胞间相互作用得以维持。然而，当慢性脑低灌注模型发生白质损伤时，分化会受到损害。因此，我们研究了星形胶质细胞和少突胶质细胞谱系细胞之间相互作用对髓鞘形成的影响，以探讨损伤的机制。在雄性 C57BL/6 小鼠中，通过在双侧颈总动脉上应用微线圈来建立体内慢性脑低灌注模型（BCAS 模型）。将CoCl2 的非致死浓度添加到来自新生大鼠皮质的原代细胞培养物中，并在体外孵育。在 BCAS 模型中，随着髓鞘减少，白质损伤进展。在手术后，OPC 和星形胶质细胞的数量增加，而 OLG 的数量在第 28 天减少。BDNF 持续减少直到第 28 天。在细胞培养的应激条件下，分化被打乱，但在含有 BDNF 的星形胶质细胞条件培养基给药后，分化得到改善。含有 BDNF 的星形胶质细胞发生分化，但由于 BDNF 的减少，在应激条件下分化受到损害。我们研究了 S100B 以探讨损伤的机制。S100B 主要由成熟的星形胶质细胞表达，具有细胞内外的神经保护和神经毒性作用。在 BCAS 模型中，胼胝体中的 GFAP 阳性星形胶质细胞增加，而成熟星形胶质细胞的数量继续减少，导致 BDNF 减少。由于 S100B 在缺血条件下的释放，成熟星形胶质细胞的减少导致 BDNF 的减少。
