IN-VITRO NEURONAL PRODUCTION AND DIFFERENTIATION BY PRECURSOR CELLS DERIVED FROM THE ADULT HUMAN FOREBRAIN
IN-VITRO NEURONAL PRODUCTION AND DIFFERENTIATION BY PRECURSOR CELLS DERIVED FROM THE ADULT HUMAN FOREBRAIN
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DOI：
10.1093/cercor/4.6.576
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发表时间：
1994-11-01
期刊：
影响因子：
3.7
通讯作者：
GOLDMAN, SA
中科院分区：
文献类型：
--
作者：
KIRSCHENBAUM, B;NEDERGAARD, M;GOLDMAN, SA
传统上认为，成年人的大脑无法进行重要的自我修复，部分原因是它无法产生新的神经元。然而，啮齿动物和鸟类在成年期被发现含有神经前体细胞。我们问是否成年人的大脑可能会保留这样的前体，培养颞叶的样本在允许神经元分化的条件下，同时暴露于H-3-胸苷。成人颞叶文化，来自皮质，皮质下，脑室周围室管膜下区（SZ），孵育7-28天，神经元和神经胶质抗原染色，放射自显影。在SZ和脑室周围白色物质的外植生长物和单层分离物中发现神经元样细胞，但在皮质中没有发现;它们表达神经元抗原，包括MAP-2、MAP-5、NF和N-CAM，并且是GFAP-。神经元对K+去极化的反应是细胞内Ca 2+的快速和可逆的增加，其增量比神经胶质细胞中的大得多。虽然大多数神经元没有H-3-胸苷标记，但少数MAP-2（+）和MAP-5（+）/GFAP-细胞确实掺入了H-3-胸苷，表明神经元是由前体有丝分裂产生的。在脑室下白色物质培养物中也发现了罕见的H-3-胸苷（+）神经元;在这些培养物中，GFAP（+）星形胶质细胞有丝分裂发生是常见的，而O 4（+）少突胶质细胞虽然是主要的细胞类型，但主要是有丝分裂后的。因此，成人前脑含有保留体外神经元产生和分化潜力的前体细胞。
It has traditionally been held that the adult brain is incapable of significant self-repair, due in part to its inability to generate new neurons. Nevertheless, rodents and birds have been found to harbor neural precursor cells in adulthood. We asked whether the adult human brain might retain such precursors, by culturing samples of temporal lobe under conditions permissive for neuronal differentiation, while exposed to H-3-thymidine. Adult human temporal lobe cultures, derived from cortex, subcortex, and periventricular subependymal zone (SZ), were incubated for 7-28 d, stained for neuronal and glial antigens, and autoradiographed. Neuron-like cells were found in explant outgrowths and monolayer dissociates of SZ and periventricular white matter, hut not cortex; they expressed neuronal antigens including MAP-2, MAP-5, NF, and N-CAM, and were GFAP-. Neurons responded to K+ depolarization with rapid and reversible increases in intracellular Ca2+, with much greater increments than those noted in glia. Although most neurons were not H-3-thymidine labeled, a small number of MAP-2(+) and MAP-5(+)/GFAP-cells did incorporate H-3-thymidine, suggesting neuronal production from precursor mitosis. Rare H-3-thymidine(+) neurons were also found in cultures of subventricular white matter; in these, GFAP(+) astrocytic mitogenesis was common, while O4(+) oligodendrocytes, although the predominant cell type, were largely postmitotic. Thus, the adult human forebrain harbors precursor cells that retain the potential for neuronal production and differentiation in vitro.