来自加州大学旧金山分校的研究人员在一系列实验中意外发现移植到新生小鼠大脑中的胚胎神经细胞能够存活,这一成果为有可能利用神经细胞移植治疗诸如阿尔茨海默氏症、癫痫、亨廷顿氏舞蹈病、帕金森氏病和精神分裂症等疾病增加了希望。

-2012年11月1日《自然》

中文翻译


【题目】发育中的皮层中间神经元受内在因素决定的细胞死亡

【译文】 皮层抑制性回路由分泌γ-氨基丁酸(GABA)的中间神经元组成,这是一类起源于胚胎腹侧前脑中大脑皮层的神经元。基于这些远端发育起源,这些皮层中间神经元的数量是如何最终被确定的,比较有趣。一种可能性,由神经营养假说表明的,即皮质中间神经元是过量的,在它们迁移至皮质中后,过量的中间神经元通过一种非固有来源的营养信号的竞争而被清除。本研究在体内、体外及移植后描述了鼠皮质中间神经元发育的细胞死亡的特征。我们发现40%的发育中的皮质中间神经元在出生后是通过Bax (Bcl-2相关X)依赖的凋亡途径清除的。当在体外培养或移植入皮质中,中间神经元前体在某一细胞阶段死亡,这类似于内源性中间神经元在正常发育阶段的死亡。超过改变200倍的移植尺度,移植细胞群体的恒定部分经历了细胞死亡。移植的神经元的死亡不会受到TrkB(原肌球蛋白激酶受体B)的细胞自主性破裂,TrkB是一种中枢神经系统中神经元所表达的主要神经营养因子受体。移植扩展了皮层中间神经元群体高达35%,但抑制性突触事件的频率不能匹配移植的中间神经元的数量。总之,我们的发现表明中间神经元细胞死亡是被内在地,细胞自主地或者通过源于其他中间神经元生存信号的群体自主竞争而决定的。

英文原稿


[Title]: Intrinsically determined cell death of developing cortical interneurons

[Authors]:Derek G. Southwell,1, 2, 3, 9 Mercedes F. Paredes,2, 4 Rui P. Galvao,2, 9 Daniel L. Jones,1, 2 Robert C. Froemke,5, 9 Joy Y. Sebe,2 Clara Alfaro-Cervello,6, 9 Yunshuo Tang,2, 3, 7 Jose M. Garcia-Verdugo,6 John L. Rubenstein,8 Scott C. Baraban1, 2 & Arturo Alvarez-Buylla1, 2

[Abstract]:Cortical inhibitory circuits are formed by γ-aminobutyric acid (GABA)-secreting interneurons, a cell population that originates far from the cerebral cortex in the embryonic ventral forebrain. Given their distant developmental origins, it is intriguing how the number of cortical interneurons is ultimately determined. One possibility, suggested by the neurotrophic hypothesis, is that cortical interneurons are overproduced, and then after their migration into cortex the excess interneurons are eliminated through a competition for extrinsically derived trophic signals. Here we characterize the developmental cell death of mouse cortical interneurons in vivo, in vitro and after transplantation. We found that 40% of developing cortical interneurons were eliminated through Bax (Bcl-2-associated X)-dependent apoptosis during postnatal life. When cultured in vitro or transplanted into the cortex, interneuron precursors died at a cellular age similar to that at which endogenous interneurons died during normal development. Over transplant sizes that varied 200-fold, a constant fraction of the transplanted population underwent cell death. The death of transplanted neurons was not affected by the cell-autonomous disruption of TrkB (tropomyosin kinase receptor B), the main neurotrophin receptor expressed by neurons of the central nervous system. Transplantation expanded the cortical interneuron population by up to 35%, but the frequency of inhibitory synaptic events did not scale with the number of transplanted interneurons. Taken together, our findings indicate that interneuron cell death is determined intrinsically, either cell-autonomously or through a population-autonomous competition for survival signals derived from other interneurons.

原文地址

http://www.nature.com/nature/journal/v491/n7422/full/nature11523.html

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