The Effects of Astrocyte and Oligodendrocyte Lineage Cell Interaction on White Matter Injury under Chronic Cerebral Hypoperfusion
The Effects of Astrocyte and Oligodendrocyte Lineage Cell Interaction on White Matter Injury under Chronic Cerebral Hypoperfusion
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DOI：
10.1016/j.neuroscience.2019.03.004
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发表时间：
2019-05
期刊：
影响因子：
3.3
通讯作者：
Shunsuke Magami;N. Miyamoto;Y. Ueno;K. Hira;R. Tanaka;K. Yamashiro;H. Oishi;H. Arai;T. Urabe;N. Hattori
中科院分区：
文献类型：
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作者：
Shunsuke Magami;N. Miyamoto;Y. Ueno;K. Hira;R. Tanaka;K. Yamashiro;H. Oishi;H. Arai;T. Urabe;N. Hattori
在白质髓鞘形成过程中，少突胶质细胞（OLGs）从少突胶质细胞前体细胞（OPCs）分化而来。这种分化是通过诸如脑源性神经营养因子（BDNF）等营养因子的细胞间相互作用来维持的。然而，在慢性脑灌注不足模型中，当白质损伤发生时，分化受损。因此，我们研究了星形胶质细胞和少突胶质细胞系细胞之间的相互作用对髓鞘形成的影响，以及损伤的机制。将微线圈置入雄性C57BL/6小鼠双侧颈总动脉，建立慢性脑内灌注不足模型（BCAS）。将非致死浓度的CoCl2加入到出生后大鼠皮层的原代细胞培养中，并在体外孵育。随着髓磷脂的减少，BCAS模型白质损伤进展。术后第28天OPCs和星形胶质细胞数量增加，OLGs数量减少。BDNF持续下降至第28天。在细胞培养的应激条件下，分化被破坏，但在给予含有BDNF的星形细胞条件培养基后，分化得到改善。含有BDNF的星形胶质细胞可以分化，但在应激条件下，由于BDNF的减少，分化受到损害。我们检查了S100B的损伤机制。S100B主要在成熟星形胶质细胞中表达，在细胞内外均具有神经保护和神经毒性作用。在BCAS模型中，胼胝体中gfap阳性的星形胶质细胞增加，而成熟星形胶质细胞数量继续减少，导致BDNF减少。缺血条件下S100B放电导致成熟星形胶质细胞减少，导致BDNF减少。
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 anin vivocerebral chronic hypoperfusion model (BCAS model). A nonlethal concentration of CoCl2 was added to the primary cell culture from the postnatal rat cortex and incubatedin 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.