Neuronal regeneration in a zebrafish model of adult brain injury.

Neuronal regeneration in a zebrafish model of adult brain injury.
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DOI:
10.1242/dmm.007336
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发表时间:
2012-03
影响因子:
4.3
通讯作者:
Sawamoto K
Sawamoto K
中科院分区:
医学2区
文献类型:
--
作者:
Kishimoto N;Shimizu K;Sawamoto K

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成年哺乳动物前脑室管膜下区(SVZ)的神经干细胞是脑损伤(如缺血性中风和创伤性脑损伤(TBI))后神经组织修复的潜在神经元来源。最近的研究表明,成年斑马鱼端脑脑室区(VZ)的神经发生与成年哺乳动物SVZ的神经发生具有共同的特征。在这里,我们建立了一个斑马鱼模型,研究损伤诱导的成年脑神经发生。我们表明,成年斑马鱼大脑具有显着的神经元再生能力。端脑损伤促进损伤半球VZ区神经元前体细胞(NPC)的增殖,与对侧半球相比。通过BrdU标记和ngn 1启动子驱动的GFP观察到的NPC的分布表明,它们侧向迁移并通过腭下和腭上到达损伤部位。当用γ-分泌酶(Notch信号通路的一种组分)抑制剂处理鱼时,到达损伤部位的NPC数量显著减少,这表明损伤诱导的神经发生机制在鱼和哺乳动物之间至少部分保守。损伤诱导的NPC在损伤后一周内在损伤部位周围的区域分化为成熟的神经元。这些细胞中的大多数表达T-box脑蛋白(Tbr 1),表明它们在该区域采用了正常的神经元命运。这些结果表明,端脑VZ有助于成年斑马鱼端脑损伤后神经组织的恢复,成年斑马鱼是一个有用的再生医学模型。
Neural stem cells in the subventricular zone (SVZ) of the adult mammalian forebrain are a potential source of neurons for neural tissue repair after brain insults such as ischemic stroke and traumatic brain injury (TBI). Recent studies show that neurogenesis in the ventricular zone (VZ) of the adult zebrafish telencephalon has features in common with neurogenesis in the adult mammalian SVZ. Here, we established a zebrafish model to study injury-induced neurogenesis in the adult brain. We show that the adult zebrafish brain possesses a remarkable capacity for neuronal regeneration. Telencephalon injury prompted the proliferation of neuronal precursor cells (NPCs) in the VZ of the injured hemisphere, compared with in the contralateral hemisphere. The distribution of NPCs, viewed by BrdU labeling and ngn1-promoter-driven GFP, suggested that they migrated laterally and reached the injury site via the subpallium and pallium. The number of NPCs reaching the injury site significantly decreased when the fish were treated with an inhibitor of γ-secretase, a component of the Notch signaling pathway, suggesting that injury-induced neurogenesis mechanisms are at least partly conserved between fish and mammals. The injury-induced NPCs differentiated into mature neurons in the regions surrounding the injury site within a week after the injury. Most of these cells expressed T-box brain protein (Tbr1), suggesting they had adopted the normal neuronal fate in this region. These results suggest that the telencephalic VZ contributes to neural tissue recovery following telencephalic injury in the adult zebrafish, and that the adult zebrafish is a useful model for regenerative medicine.
DOI: 10.1159/000090755
发表时间: 2006-01-01
影响因子: 2.9
作者:
Givogri, MI;de Planell, M;Bongarzone, ER
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DOI: 10.1016/s0165-3806(01)00193-6
发表时间: 2001-09-23
期刊: DEVELOPMENTAL BRAIN RESEARCH
影响因子: --
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发表时间: 2005-01-18
影响因子: 11.1
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通讯作者: DeArmond, SJ