Progenitor cells from the adult mouse brain acquire a neuronal phenotype in response to β-amyloid

Progenitor cells from the adult mouse brain acquire a neuronal phenotype in response to β-amyloid
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DOI:
10.1016/j.neurobiolaging.2005.03.019
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发表时间:
2006-04-01
影响因子:
4.2
通讯作者:
Copani, A
Copani, A
中科院分区:
医学2区
文献类型:
--
作者:
Calafiore, M;Battaglia, G;Copani, A

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成年小鼠脑室下区神经球在悬浮培养中培养12-15天。神经球主要由巢蛋白免疫反应阳性的神经前体细胞组成,也含有巢蛋白阴性前体。我们使用这些神经球来确定合成的β-淀粉样蛋白片段(βAP(1-42)和βAP(25-35))对鼻咽癌增殖、分化和生存的影响。我们发现,暴露在25MUβAP(25-35)或βAP(1-42)中24个it(对成熟神经元的毒性条件)的神经球没有发生细胞凋亡。相反,βAP(25-35)将巢蛋白阴性的前体定向为巢蛋白阳性的神经前体细胞,并将巢蛋白阳性的神经前体细胞转化为神经母细胞。侧脑室注入全长βAP(1-42)可增加SVZ内PSA-NCAM阳性细胞的数量,但不影响细胞增殖。我们的结论是,βAP影响祖细胞的命运,推动它们向神经元分化。(C)2005 Elsevier Inc.保留所有权利。
Neurospheres from adult mouse subventricular zone (SVZ) were grown in suspension cultures for 12-15 days. Neurospheres consisted mainly of neural precursor cells (NPCs) immunoreactive for nestin and also contained nestin-negative precursors. We used these neurospheres to determine the effects of synthetic beta-amyloid fragments (both beta AP(1-42) and beta AP(25-35)) on NPC proliferation, differentiation and survival. We show that neurospheres exposed to 25 mu M beta AP(25-35) or beta AP(1-42) for 24 It (a toxic condition for mature neurons) did not undergo apoptosis. Instead, beta AP(25-35) orientated nestin-negative precursors towards nestin-positive NPCs and turned nestin-positive NPCs into neuroblasts. Intracerebroventricular infusion of full-length beta AP(1-42) increased the population of PSA-NCAM-positive cells in the SVZ, without affecting proliferation. We conclude that beta AP influences the fate of progenitor cells, driving their differentiation towards a neuronal lineage. (C) 2005 Elsevier Inc. All rights reserved.