Glutathione peroxidase overexpression does not rescue impaired neurogenesis in the injured immature brain.
Glutathione peroxidase overexpression does not rescue impaired neurogenesis in the injured immature brain.
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DOI：
10.1002/jnr.21996
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发表时间：
2009-06
影响因子：
4.2
通讯作者：
Noble-Haeusslein, Linda J.
中科院分区：
文献类型：
--
作者：
Potts, Matthew B.;Rola, Radoslaw;Claus, Catherine P.;Ferriero, Donna M.;Fike, John R.;Noble-Haeusslein, Linda J.
创伤性脑损伤是幼儿残疾的主要原因，并与长期认知缺陷有关。这些临床发现促使研究海马在实验模型的创伤，以发育中的大脑在出生后的一天（p21）。以前使用这种模型的研究已经揭示了海马体中神经元的逐渐丧失，因为脑损伤的动物成熟到年轻成年。在这里，我们确定这种海马的脆弱性是否同样反映在改变神经发生，如果抗氧化剂谷胱甘肽过氧化物酶（GPx）调节神经发生在受伤的，不成熟的大脑成熟。对过表达谷胱甘肽过氧化物酶（GPx）的雄性转基因小鼠和野生型同窝小鼠进行p21的受控皮质撞击或假手术。伤后2周，分别用Ki-67和doublecortin测定颗粒下带内增殖细胞和未成熟神经元的数量。损伤后两周开始，用溴脱氧尿苷（BrdU）标记分裂细胞。4周后用共聚焦显微镜测量存活率（BrdU+）和神经元分化（BrdU+/NeuN+）。双因素方差分析显示，基因型和损伤之间没有显着的相互作用。然而，随后对损伤和基因型个体效应的分析显示，损伤后2周颗粒下区增殖（Ki-67）（p=0.0003）和损伤后6周前体细胞存活（BrdU+）（p=0.016）显著减少，损伤后6周神经元分化（BrdU+/NeuN+）呈减少趋势（p=0.087）。总的来说，这些数据表明，创伤性损伤损伤未成熟的大脑损害成熟过程中的神经发生，并表明GPx不能挽救这种减少的神经发生。
Traumatic brain injury (s) is a leading cause of disability among young children and is associated with long-term cognitive deficits. These clinical findings have prompted an investigation of the hippocampus in an experimental model of trauma to the developing brain at postnatal day (p21). Previous studies using this model have revealed a progressive loss of neurons in the hippocampus as brain-injured animals mature to young adulthood. Here we determine if this hippocampal vulnerability is likewise reflected in altered neurogenesis and if the antioxidant glutathione peroxidase (GPx) modulates neurogenesis during maturation of the injured, immature brain. Male transgenic mice that overexpress glutathione peroxidase (GPx) and wildtype littermates were subjected to controlled cortical impact or sham surgery on p21. At two weeks postinjury, the numbers of proliferating cells and immature neurons within the subgranular zone were measured using Ki-67 and doublecortin, respectively. Bromodeoxyuridine (BrdU) was used to label dividing cells beginning two weeks postinjury. Survival (BrdU+) and neuronal differentiation (BrdU+/NeuN+) were then measured four weeks later with confocal microscopy. Two-way ANOVA revealed no significant interaction between genotype and injury. Subsequent analysis of the individual effects of injury and genotype, however, showed a significant reduction in subgranular zone proliferation (Ki-67) at two weeks postinjury (p=0.0003) and precursor cell survival (BrdU+) at six weeks postinjury (p=0.016) and a trend towards reduced neuronal differentiation (BrdU+/NeuN+) at six weeks postinjury (p=0.087). Overall, these data demonstrate that traumatic injury to the injured immature brain impairs neurogenesis during maturation and suggest that GPx cannot rescue this reduced neurogenesis.
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