Developmental Toxicology Laboratory, Department of Medical Elementology & Toxicology, Jamia Hamdard (Hamdard University), New Delhi, India-110062.
Brain Res. 2011 Jan 31;1371:140-9. doi: 10.1016/j.brainres.2010.11.050. Epub 2010 Nov 19.
Cytokinetics regulating cell cycle division can be modulated by several endogenous factors. EAE (experimental autoimmune encephalomyelitis) increases proliferation of progenitor cells in the subventricular zone (SVZ). Using cumulative and single S phase labeling with 5-bromo-2-deoxyuridine, we examined cell cycle kinetics of neural progenitor cells in the SVZ after EAE. 20% of the SVZ cell population was proliferating in adjuvant control rats. However, EAE significantly increased them up to 27% and these cells had a cell cycle length (TC) of 15.6h, significantly (P<0.05) shorter than the 19 h TC in non EAE SVZ cells. Few TUNEL (+) cells were detected in the SVZ cells of adjuvant controls. EAE increased (P<0.05) TUNEL (+) nuclei in SVZ suggesting early stage progenitor cell death. Cell cycle phase analysis revealed that EAE substantially shortened the length of the G1 phase (9.6h) compared with the G1 phase of 12.25 h in adjuvant control SVZ cells (P<0.05). This reduction in G1 contributes to EAE-induced reduction of TC because no significant changes were detected on the length of S, G2 and M phases between the two groups. Our results show a surge in proliferating progenitor cells in the SVZ with concomitant increase in apoptotic cell death after EAE. Furthermore, increase in the SVZ proliferation contributes to EAE-induced neurogenesis and this increase is regulated by shortening the G1 phase. Our investigation suggests the activation of quiescent cells in SVZ to generate actively proliferating progenitors. Moreover, the increase in the cell death in proliferating population may contribute towards negative regulation of proliferative cell number and hence diminished regenerative capacity of CNS following EAE.
细胞周期分裂的细胞因子可以被几种内源性因素调节。EAE（实验性自身免疫性脑脊髓炎）增加了脑室下区（SVZ）祖细胞的增殖。我们使用 5-溴-2-脱氧尿苷的累积和单一 S 期标记，研究了 EAE 后 SVZ 中的神经祖细胞的细胞周期动力学。在佐剂对照大鼠中，有 20%的 SVZ 细胞群体在增殖。然而，EAE 显著增加了它们的数量，达到 27%，这些细胞的细胞周期长度（TC）为 15.6 小时，明显（P<0.05）短于非 EAE SVZ 细胞的 19 小时 TC。在佐剂对照的 SVZ 细胞中很少检测到 TUNEL（+）细胞。EAE 增加了 SVZ 中的 TUNEL（+）核（P<0.05），表明早期祖细胞死亡。细胞周期相分析显示，EAE 显著缩短了 G1 期的长度（9.6 小时），与佐剂对照 SVZ 细胞的 G1 期（12.25 小时）相比（P<0.05）。这种 G1 的减少导致了 EAE 诱导的 TC 减少，因为在两组之间，S、G2 和 M 期的长度没有发生显著变化。我们的结果显示，EAE 后 SVZ 中增殖祖细胞激增，同时凋亡细胞死亡增加。此外，SVZ 增殖的增加有助于 EAE 诱导的神经发生，这种增加是通过缩短 G1 期来调节的。我们的研究表明，SVZ 中的静止细胞被激活，产生活跃增殖的祖细胞。此外，增殖群体中细胞死亡的增加可能有助于对增殖细胞数量的负调节，从而降低 EAE 后中枢神经系统的再生能力。
