Reduced Proliferation of Oligodendrocyte Progenitor Cells in the Postnatal Brain of Dystonia Musculorum Mice
Reduced Proliferation of Oligodendrocyte Progenitor Cells in the Postnatal Brain of Dystonia Musculorum Mice
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DOI：
10.1007/s11064-017-2342-5
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发表时间：
2017
影响因子：
4.4
通讯作者：
M. I. Hossain;M. Horie;H. Takebayashi
中科院分区：
文献类型：
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作者：
M. I. Hossain;M. Horie;H. Takebayashi
肌张力障碍（dt）小鼠表现出感觉神经变性和运动障碍，例如肌张力障碍和小脑共济失调。致病基因Dystonin（Dst）编码细胞骨架连接蛋白。虽然感觉神经变性已经得到了很好的研究，在中枢神经系统（CNS）的胶质细胞反应知之甚少。在此，我们使用新一代原位杂交（ISH）探针Ki-67和增殖细胞核抗原（PCNA）探针研究了DstG纯合子小鼠CNS中的细胞增殖，这两种探针都能有效地检测增殖细胞。结果发现，出生后21天（P21），大鼠大脑胼胝体和丘脑中Ki-67阳性细胞明显减少。在出生后14天（P14），脑内也有类似的趋势，但不显著。PCNAISH和Ki-67免疫组化结果也证实了细胞增殖减少。细胞类型特异性标记物的双重染色显示，在野生型和dtbrain中增殖的细胞都是少突胶质祖细胞（OPCs）。我们还观察到在P21时DstG突变小鼠胼胝体中Olig 2阳性细胞数量减少，表明增殖减少导致OPC数量减少。我们的数据表明，OPCs增殖减少在thedt小鼠脑在出生后阶段，它随后导致OPCs的数量减少。
Dystonia musculorum(dt) mice show sensory neurodegeneration and movement disorder, such as dystonia and cerebellar ataxia. The causative geneDystonin(Dst) encodes a cytoskeleton linker protein. Although sensory neurodegeneration has been well studied, glial cell responses in the central nervous system (CNS) are poorly understood. Here, we investigated cell proliferation in the CNS ofDstGthomozygous mice using newly generatedin situhybridization (ISH) probes—Ki-67andproliferating cell nuclear antigen(PCNA)probes—both of which effectively detect proliferating cells. We found thatKi-67-positive cells were significantly decreased in the corpus callosum and thalamus ofdtbrain at postnatal day 21 (P21). There is a similar but not significant tendency at postnatal day 14 (P14) in thedtbrain. We also confirmed the reduced proliferation byPCNAISH and Ki-67 immunohistochemistry. Double staining with cell-type-specific markers revealed that proliferating cells are oligodendrocyte progenitor cells (OPCs) in both wild-type anddtbrain. We also observed a reduced number of Olig2-positive cells in the corpus callosum ofDstGthomozygous mice at P21, indicating that reduced proliferation resulted in a reduced number of OPCs. Our data indicate that OPCs proliferation is reduced in thedtmouse brain at the postnatal stage and that it subsequently results in the reduced number of OPCs.