Unbiased stereological analysis of the fate of oligodendrocyte progenitor cells in the adult mouse brain and effect of reference memory training

Unbiased stereological analysis of the fate of oligodendrocyte progenitor cells in the adult mouse brain and effect of reference memory training
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DOI:
10.1016/j.bbr.2017.04.027
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发表时间:
2017-06-30
影响因子:
2.7
通讯作者:
Messier, Claude
Messier, Claude
中科院分区:
心理学3区
文献类型:
--
作者:
Boulanger, Jenna J.;Messier, Claude

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少突胶质细胞祖细胞(OPCs)是在出生后早期分化为髓鞘少突胶质细胞的胶质细胞。然而,OPCs在发育髓鞘形成之后仍然存在,并且代表了成人大脑灰质和白质中重要的循环细胞群。在此,我们采用无偏系统体视学分析来确定成年小鼠新皮层和胼胝体中OPCs的总数。我们发现,在成人新皮层中,OPCs与神经元的比例为1:10。同样,皮层中OPCs与少突胶质细胞的比例为1:1,胼胝体中为1:7。我们还使用BrdU标记和NG2-CreER (TM):EYFP报告小鼠来确定成年OPCs的增殖比例及其命运。我们发现,OPCs在成年期继续分化为少突胶质细胞,白质OPCs比灰质OPCs更有可能分化为少突胶质细胞表型。OPC向少突胶质细胞表型的分化既可以由OPC自发分化直接发生,也可以在OPC细胞分裂后发生。我们也为成人皮层灰质的OPCs的神经元分化提供了证据。尽管活动依赖的神经网络活动被假设为OPC增殖和分化的调节剂,但我们发现参考记忆训练并不影响成年小鼠大脑中增殖和分化的OPC的比例。
Oligodendrocyte progenitor cells (OPCs) are glial cells that differentiate into myelinating oligodendrocytes during early stages of post-natal life. However, OPCs persist beyond developmental myelination and represent an important population of cycling cells in the gray and white matter of the adult brain. Here, we used unbiased systematic stereological analysis to determine the total number of OPCs in the neocortex and corpus callosum of the adult mouse. We found that the ratio of OPCs to neurons is of 1:10 in the adult neocortex. Likewise, the ratio of OPCs to oligodendrocytes is of 1:1 in the cortex and 1:7 in the corpus callosum. We also used BrdU labeling and the NG2-CreER (TM):EYFP reporter mouse to determine the proportion of proliferating adult OPCs and their fate. We show that OPCs continue to differentiate into oligodendrocytes in adulthood, with white matter OPCs being more likely to differentiate into an oligodendrocyte phenotype than gray matter OPCs. The differentiation of OPCs into an oligodendrocyte phenotype can occur either directly from a spontaneous differentiation by an OPC or following OPC cell division. We also provide evidence for the neuronal differentiation of adult OPCs in the cortical gray matter. Although activity-dependent neural network activity has been hypothesized to serve as a modulator of OPC proliferation and differentiation, we found that reference memory training did not affect the proportion of proliferating and differentiated OPCs in the adult mouse brain.