Repeated injuries dramatically affect cells of the oligodendrocyte lineage: Effects of PDGF and NT-3 in vitro
Repeated injuries dramatically affect cells of the oligodendrocyte lineage: Effects of PDGF and NT-3 in vitro
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DOI：
10.1002/glia.20136
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发表时间：
2005-03-01
期刊：
影响因子：
6.2
通讯作者：
Fressinaud, C
中科院分区：
文献类型：
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作者：
Fressinaud, C
在多发性硬化症中，发生复发并且髓鞘再生不完全，而大鼠中由溶血磷脂酰胆碱（LPC）诱导的一个脱髓鞘病变完全髓鞘再生;血小板衍生生长因子（PDGF）加速该过程（Allamargot等人：Brain Res 918：28-39，2001）和神经营养因子-3（NT-3）（Jean等人：Brain Res 972：110-118，2003）。同样，少突胶质细胞（OL）祖细胞可能不会因两到三次毒性脱髓鞘而耗尽（Penderis等人：Brain 126：1382-1391，2003）;然而，这不允许关于驻留细胞（成熟OL）的命运的结论。由于在慢性MS斑块中每OL的有髓纤维不断减少（Fressinaud和Jean：J Neurochem 85（suppl）：100，2003），这表明OL合成新髓鞘膜的能力降低可能是由于连续复发，从而损害髓鞘再生。因此，我们已经确定了多重与单一LPC处理对新生大鼠脑纯OL培养物的影响（Fressinaud和Vallat：J Neurosci Res 38：202-213，1994），以及PDGF和NT-3在这些条件下的推定的促髓鞘再生作用。分裂（0.5（.）10（-5）M，6 h x 4）和多发性（2（.）10（-5）M，24 h x 2）LPC剂量诱导的细胞损失比单一处理（2 X 10-5 M，24 h）更多，且无恢复。OL祖细胞（A2 B5+细胞）和分化的（CNP+）OL急剧减少。此外，成熟的（MBP+）OL从这些培养物中消失，表明成熟的OL也容易受到多重损伤。PDGF，以及NT-3，诱导至少部分恢复，并增强OL祖细胞增殖。在这些生长因子处理的文化，成熟的OL代表四分之一的细胞，并延长了许多分支的过程和推定的髓鞘球。(C)2004威利-利斯公司
In multiple sclerosis, relapses occur and remyelination is incomplete, whereas one demyelinating lesion induced by lysophosphatidyl choline (LPC) in rats is completely remyelinated; this process is accelerated by platelet-derived growth factor (PDGF) (Allamargot et al.: Brain Res 918:28-39, 2001) and neurotrophin-3 (NT-3) (Jean et al.: Brain Res 972:110-118, 2003). Similarly, oligodendrocyte (OL) progenitors might not be depleted by two to three episodes of toxic demyelination (Penderis et al.: Brain 126:1382-1391, 2003); nevertheless this does not allow conclusions about the fate of resident cells (mature OL). As myelinated fibers per OL are constantly decreased in chronic MS plaques (Fressinaud and Jean: J Neurochem 85(suppl):100, 2003), this suggests that OL decreased capability to synthesize new myelin membranes could result from successive relapses, impairing thereby remyelination. Thus, we have determined the consequences of multiple versus unique (Fressinaud and Vallat: J Neurosci Res 38:202-213, 1994) LPC treatments on newborn rat brain pure OL cultures, as well as the putative pro-remyelinating effects of PDGF and of NT-3 in these conditions. Split (0.5 (.) 10(-5) M, 6 h x 4) and multiple (2 (.) 10(-5) M, 24 h x 2) LPC doses induced more cell loss than a unique treatment (2 X 10-5 M, 24 h) and there was no recovery. OL progenitors (A2B5+ cells) and differentiated (CNP+) OL were drastically decreased. Moreover, mature (MBP+) OL disappeared from these cultures, indicating that mature OL are also vulnerable to multiple insults. PDGF, as well as NT-3, induced at least partial recovery, and enhanced OL progenitor proliferation. In cultures treated with either of these growth factors, mature OL represented one-fourth of cells and extended numerous ramified processes and putative myelin balls. (C) 2004 Wiley-Liss, Inc.