Increased NG2+ glial cell proliferation and oligodendrocyte generation in the hypomyelinating mutant shiverer
Increased NG2+ glial cell proliferation and oligodendrocyte generation in the hypomyelinating mutant shiverer
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DOI：
10.1002/glia.20055
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发表时间：
2004-10-01
期刊：
影响因子：
6.2
通讯作者：
Nishiyama, A
中科院分区：
文献类型：
--
作者：
Bu, J;Banki, A;Nishiyama, A
表达NG2蛋白聚糖的神经胶质细胞（NG2（+）细胞）被认为是中枢神经系统（CNS）中的少突胶质细胞祖细胞（OPC），基于它们在体外产生成熟少突胶质细胞的能力。为了了解髓鞘发育不良的条件如何影响OPC的增殖和分化，我们研究了NG2（+）OPC在shiverer突变体（shi）体内的增殖和分化，由于髓鞘碱性蛋白基因的缺失，这些突变体不能形成致密的髓鞘。急性溴脱氧尿苷（BrdU）标记研究显示，在出生后18天（P18）和P60之间，shi脊髓中NG2（+）细胞增殖增加4至6倍，并且大多数BrdU（+）细胞在P18之后为NG2（+）。增加的增殖伴随着OPC和少突胶质细胞数量的2倍增加。在P18单次注射BrdU后的存活研究显示，随着时间的推移，BrdU（+）/NG2（+）细胞数量下降，同时BrdU（+）少突胶质细胞数量增加，这表明增殖的NG2（+）细胞已分化为少突胶质细胞。BrdU。少突胶质细胞在SHI脊髓中产生的时间较长，并且在SHI中比在野生型脊髓中持续的时间更长。这些发现表明，新的少突胶质细胞继续产生在髓鞘发育不良的shi脊髓增强的增殖和分化的NG2（+）少突胶质细胞祖细胞。(C)2004 Wiley-Liss，Inc.
Glial cells that express the NG2 proteoglycan (NG2(+) cells) are considered to be oligodendrocyte progenitors (OPCs) in the central nervous system (CNS), based on their ability to give rise to mature oligodendrocytes in vitro. To understand how dysmyelinated conditions influence OPC proliferation and differentiation, we studied proliferation and differentiation of NG2(+) OPCs in vivo in the shiverer mutant (shi), which do not form compact myelin due to a deletion in the myelin basic protein gene. Acute bromodeoxyuridine (BrdU) labeling studies revealed a 4- to 6-fold increase in NG2(+) cell proliferation in shi spinal cord between postnatal day18 (P18) and P60, and most BrdU(+) cells were NG2(+) after P18. The increased proliferation was accompanied by a 2-fold increase in the number of OPCs and oligodendrocytes. Survival studies following a single injection of BrdU at P18 revealed a decline in the number of BrdU(+)/NG2(+) cells with a concomitant increase in the number of BrdU(+) oligodendrocytes over time, suggesting that the proliferated NG2(+) cells had differentiated into oligodendrocytes. BrdU. oligodendrocytes were generated over a longer period of time in shi spinal cord and persisted longer in shi than in wild type spinal cord. These findings suggest that new oligodendrocytes continue to be generated in the dysmyelinated shi spinal cord by enhanced proliferation and differentiation of NG2(+) oligodendrocyte progenitor cells. (C) 2004 Wiley-Liss, Inc.