An organotypic slice culture model of chronic white matter injury with maturation arrest of oligodendrocyte progenitors.
An organotypic slice culture model of chronic white matter injury with maturation arrest of oligodendrocyte progenitors.
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DOI：
10.1186/1750-1326-6-46
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发表时间：
2011-07-05
影响因子：
15.1
通讯作者：
Back SA
中科院分区：
文献类型：
--
作者：
Dean JM;Riddle A;Maire J;Hansen KD;Preston M;Barnes AP;Sherman LS;Back SA
中枢神经系统髓鞘形成障碍通常发生在神经发育和成人神经疾病的慢性白质病变中。最近的研究支持髓鞘失败可能涉及一种被破坏的细胞修复机制，在弥漫性星形胶质细胞增生症的皮损中，少突胶质细胞(OL)前体细胞(OPC)增殖，但无法完全分化为成熟的髓鞘OL。目前还没有复制这些髓鞘形成失败特征的体外模型。取出生后0.5/1龄大鼠前脑冠状切片，体外培养1、5、9天。切片迅速显示弥漫性星形胶质细胞增生和细胞外基质糖胺聚糖透明质酸(HA)的积聚，HA是OPC分化和再髓鞘形成的抑制物。在1DIV时~1.5%的寡核苷酸表达caspase-3活性，到9DIV时caspase-3活性增加到~11.5%。1DIV时PDGFRα+和α+/Ki67+OPC密度较0DIV时显著升高(P<0.01)。尽管有这种增殖反应，9DIV~60%的白质OL是晚期祖细胞(PreOls)，而出生后第10天的白质OL约为7%(P<；0.0001)，这与Preol成熟停滞一致。切片中加入透明质酸后，9DIV时MBP+OL的密度显著低于对照组(分别为217vs.328±17个/mm~2；P=0.0003)，支持HA在慢性病变OL谱系发展中的抑制作用。弥漫性白质星形胶质细胞增生症和早期OPC增殖伴OL成熟受损在该髓鞘衰竭模型中再现。该系统可用于确定与星形胶质细胞增多症和透明质酸蓄积相关的OPC成熟停滞和髓鞘形成障碍的机制。
CNS myelination disturbances commonly occur in chronic white matter lesions in neurodevelopmental and adult neurological disorders. Recent studies support that myelination failure can involve a disrupted cellular repair mechanism where oligodendrocyte (OL) progenitor cells (OPCs) proliferate in lesions with diffuse astrogliosis, but fail to fully differentiate to mature myelinating OLs. There are no in vitro models that reproduce these features of myelination failure. Forebrain coronal slices from postnatal day (P) 0.5/1 rat pups were cultured for 1, 5, or 9 days in vitro (DIV). Slices rapidly exhibited diffuse astrogliosis and accumulation of the extracellular matrix glycosaminoglycan hyaluronan (HA), an inhibitor of OPC differentiation and re-myelination. At 1 DIV ~1.5% of Olig2+ OLs displayed caspase-3 activation, which increased to ~11.5% by 9 DIV. At 1 DIV the density of PDGFRα+ and PDGFRα+/Ki67+ OPCs were significantly elevated compared to 0 DIV (P < 0.01). Despite this proliferative response, at 9 DIV ~60% of white matter OLs were late progenitors (preOLs), compared to ~7% in the postnatal day 10 rat (P < 0.0001), consistent with preOL maturation arrest. Addition of HA to slices significantly decreased the density of MBP+ OLs at 9 DIV compared to controls (217 ± 16 vs. 328 ± 17 cells/mm2, respectively; P = 0.0003), supporting an inhibitory role of HA in OL lineage progression in chronic lesions. Diffuse white matter astrogliosis and early OPC proliferation with impaired OL maturation were reproduced in this model of myelination failure. This system may be used to define mechanisms of OPC maturation arrest and myelination failure related to astrogliosis and HA accumulation.
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DOI：
10.1523/jneurosci.5524-09.2011
发表时间：
2011-04-20
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Wang Y;Cheng X;He Q;Zheng Y;Kim DH;Whittemore SR;Cao QL
通讯作者：
Cao QL
DOI：
10.1073/pnas.1006496107
发表时间：
2010-06-22
影响因子：
11.1
作者：
Sloane, J. A.;Batt, C.;Vartanian, T.
通讯作者：
Vartanian, T.
影响因子：
5.3
作者：
Craig, A;Luo, NL;Back, SA
通讯作者：
Back, SA
影响因子：
2.9
作者：
Huang, Zhiheng;Liu, Jiangqin;Chen, Chao
通讯作者：
Chen, Chao
影响因子：
82.9
作者：
John, GR;Shankar, SL;Brosnan, CF
通讯作者：
Brosnan, CF