干细胞移植恢复大脑记忆

  近日,复旦大学张素春团队首次将人类胚胎干细胞成功转化成特定的神经细胞,并将转化后的中间细胞注入到小鼠大脑中,使已丧失学习和记忆功能的小鼠恢复了学习和记忆能力。近日,相关研究成果发表于最新一期的学术期刊《Nature Biotechnol 自然 生物技术》。业内专家认为,该成果对治愈各种神经功能缺陷疾病有重大意义。
        据介绍,张素春科研团队选中了一种不会排斥其他物种移植物的特殊小鼠,他们首先“蓄意破坏”了小鼠大脑中掌管“学习和记忆”、被称为“内侧隔核”的大脑区域的“线路”,使小鼠暂时丧失“学习和记忆”能力。
        然后,研究人员利用化学方法将人类胚胎干细胞转化成神经细胞,并将这些转化后的中间细胞移植到小鼠大脑中。张素春说,这一过程有点类似于拆除一段电话线,之后你如果能找到正确的线路,需要时就能够把“断线”接上。
        于是,研究人员将细胞移植到了小鼠记忆回路的另一端――大脑记忆中心海马内。植入后的干细胞立刻形成两种常见的、重要的神经元类型,它们分别与化学物质γ-氨基丁酸或乙酰胆碱能神经元进行有效沟通,并响应来自大脑的化学指令,开始特化并与海马中的适当细胞相连接。
        测试证实,这些接受干细胞移植后“连接”成功的小鼠,常规学习和记忆能力得到了有效恢复,评分明显优于那些依然丧失“学习和记忆”能力的小鼠。
        该研究的终极目标是通过细胞替代来修复大脑损伤并将有可能马上应用于构建药物筛查的模型,并为将来治愈各种神经功能缺陷疾病带来希望。

推荐原文阅读:
Nat Biotechnol. 2013 May;31(5):440-7. doi: 10.1038/nbt.2565. Epub 2013 Apr 21.
Medial ganglionic eminence-like cells derived from human embryonic stem cells correct learning and memory deficits.
Liu Y, Weick JP, Liu H, Krencik R, Zhang X, Ma L, Zhou GM, Ayala M, Zhang SC.
SourceWaisman Center, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA.
Abstract
Dysfunction of basal forebrain cholinergic neurons (BFCNs) and γ-aminobutyric acid (GABA) interneurons, derived from medial ganglionic eminence (MGE), is implicated in disorders of learning and memory. Here we present a method for differentiating human embryonic stem cells (hESCs) to a nearly uniform population of NKX2.1(+) MGE-like progenitor cells. After transplantation into the hippocampus of mice in which BFCNs and some GABA neurons in the medial septum had been destroyed by mu P75-saporin, human MGE-like progenitors, but not ventral spinal progenitors, produced BFCNs that synaptically connected with endogenous neurons, whereas both progenitors generated similar populations of GABA neurons. Mice transplanted with MGE-like but not spinal progenitors showed improvements in learning and memory deficits. These results suggest that progeny of the MGE-like progenitors, particularly BFCNs, contributed to learning and memory. Our findings support the prospect of using human stem cell-derived MGE-like progenitors in developing therapies for neurological disorders of learning and memory.