The Effect of Pro-Neurogenic Gene Expression on Adult Subventricular Zone Precursor Cell Recruitment and Fate Determination After Excitotoxic Brain Injury.

IF 1.1 Q4 CELL & TISSUE ENGINEERING
Journal of Stem Cells & Regenerative Medicine Pub Date : 2016-05-30 eCollection Date: 2016-01-01
Kathryn S Jones, Bronwen J Connor
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Abstract

Despite the presence of on-going neurogenesis in the adult mammalian brain, neurons are generally not replaced after injury. Using a rodent model of excitotoxic cell loss and retroviral (RV) lineage tracing, we previously demonstrated transient recruitment of precursor cells from the subventricular zone (SVZ) into the lesioned striatum. In the current study we determined that these cells included migratory neuroblasts and oligodendrocyte precursor cells (OPC), with the predominant response from glial cells. We attempted to override this glial response by ectopic expression of the pro-neurogenic genes Pax6 or Dlx2 in the adult rat SVZ following quinolinic acid lesioning. RV-Dlx2 over-expression stimulated repair at a previously non-neurogenic time point by enhancing neuroblast recruitment and the percentage of cells that retained a neuronal fate within the lesioned area, compared to RV-GFP controls. RV-Pax6 expression was unsuccessful at inhibiting glial fate and intriguingly, increased OPC cell numbers with no change in neuronal recruitment. These findings suggest that gene choice is important when attempting to augment endogenous repair as the lesioned environment can overcome pro-neurogenic gene expression. Dlx2 over-expression however was able to partially overcome an anti-neuronal environment and therefore is a promising candidate for further study of striatal regeneration.

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Abstract Image

前神经源性基因表达对兴奋性脑损伤后成人室下带前体细胞募集及命运决定的影响。
尽管在成年哺乳动物大脑中存在持续的神经发生,但神经元在损伤后通常不会被替换。利用啮齿动物兴奋性毒性细胞丢失模型和逆转录病毒(RV)谱系追踪,我们先前证明了前体细胞从室下区(SVZ)短暂募集到受损纹状体。在目前的研究中,我们确定这些细胞包括移行性神经母细胞和少突胶质细胞前体细胞(OPC),主要反应来自胶质细胞。我们试图通过异位表达前神经发生基因Pax6或Dlx2在成年大鼠SVZ在喹啉酸损伤后覆盖这种胶质反应。与RV-GFP对照相比,RV-Dlx2过表达通过增强神经母细胞募集和损伤区域内保留神经元命运的细胞百分比,刺激了先前非神经源性时间点的修复。RV-Pax6的表达没有成功抑制胶质细胞的命运,有趣的是,OPC细胞数量增加,神经元募集没有变化。这些发现表明,当试图增强内源性修复时,基因选择是重要的,因为受损环境可以克服前神经源性基因的表达。然而,Dlx2的过表达能够部分克服抗神经元环境,因此是纹状体再生进一步研究的有希望的候选者。
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来源期刊
CiteScore
3.40
自引率
0.00%
发文量
5
审稿时长
14 weeks
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