Gordon R J, Tattersfield A S, Vazey E M, Kells A P, McGregor A L, Hughes S M, Connor B
Department of Pharmacology and Clinical Pharmacology, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand.
Neuroscience. 2007 Jun 8;146(4):1704-18. doi: 10.1016/j.neuroscience.2007.03.011. Epub 2007 Apr 24.
A number of studies have demonstrated directed migration of neural progenitor cells to sites of brain injury and disease, however a detailed examination of when a cell is "born" in relation to injury induction and the migratory response of that cell has not previously been determined. This study therefore examined the temporal correlation between progenitor cell proliferation ("birth") and neuroblast migratory response into the damaged striatum following quinolinic acid (QA) lesioning of the adult rat striatum. Retroviral labeling of subventricular zone (SVZ)-derived progenitor cells demonstrated that cell loss in the QA-lesioned striatum increased progenitor cell migration through the rostral migratory stream (RMS) for up to 30 days. In addition, a population of dividing cells originating from the SVZ generated doublecortin positive neuroblasts that migrated into the damaged striatum in response to cell loss invoked by the QA lesion. Quantification of bromodeoxyuridine (BrdU)-labeled cells co-expressing doublecortin revealed that the majority of cells present in the damaged striatum were generated from progenitor cells dividing within 2 days either prior to or following the QA lesion. In contrast, cells dividing 2 or more days following QA lesioning, migrated into the striatum and exhibited a glial phenotype. These results demonstrate that directed migration of SVZ-derived cells and neuroblast differentiation in response to QA lesioning of the striatum is acute and transient. We propose this is predominantly due to a reduced capacity over time for newly generated neuroblasts to respond to the lesioned environment due to a loss or inhibition of migratory cues.
多项研究已证明神经祖细胞可定向迁移至脑损伤和疾病部位，然而，此前尚未确定细胞“诞生”时间与损伤诱导以及该细胞迁移反应之间的详细关系。因此，本研究考察了成年大鼠纹状体经喹啉酸（QA）损伤后，祖细胞增殖（“诞生”）与神经母细胞向受损纹状体迁移反应之间的时间相关性。对源自脑室下区（SVZ）的祖细胞进行逆转录病毒标记显示，QA损伤的纹状体中的细胞损失使祖细胞通过吻侧迁移流（RMS）的迁移增加，持续长达30天。此外，一群源自SVZ的分裂细胞产生了双皮质素阳性神经母细胞，这些神经母细胞响应QA损伤引起的细胞损失而迁移到受损纹状体中。对共表达双皮质素的溴脱氧尿苷（BrdU）标记细胞进行定量分析发现，受损纹状体中存在的大多数细胞是由在QA损伤前或损伤后2天内分裂的祖细胞产生的。相比之下，QA损伤后2天或更长时间分裂的细胞迁移到纹状体并表现出神经胶质细胞表型。这些结果表明，源自SVZ的细胞的定向迁移以及对纹状体QA损伤的神经母细胞分化是急性和短暂的。我们认为，这主要是由于随着时间的推移，新产生的神经母细胞对受损环境的反应能力下降，原因是迁移线索的丧失或抑制。
