Effects of altered levels of extracellular superoxide dismutase and irradiation on hippocampal neurogenesis in female mice.

Effects of altered levels of extracellular superoxide dismutase and irradiation on hippocampal neurogenesis in female mice.
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DOI:
10.1016/j.ijrobp.2013.08.002
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发表时间:
2013-11-15
影响因子:
7
通讯作者:
Huang, Ting-Ting
Huang, Ting-Ting
中科院分区:
医学1区
文献类型:
--
作者:
Zou, Yani;Leu, David;Chui, Jennifer;Fike, John R.;Huang, Ting-Ting

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细胞外超氧化物歧化酶 (EC-SOD) 水平的改变和颅脑照射已被证明会影响海马神经发生。然而,之前的研究仅在雄性小鼠中进行,尚不清楚雄性和雌性之间是否存在差异。因此,对雌性小鼠进行了研究,并将结果与​​早期研究中雄性小鼠的结果进行了比较。雌性野生型 (WT)、EC-SOD 无效 (KO) 和具有 EC-SOD 神经元特异性表达 (OE) 的 EC-SOD 双基因小鼠在 8 周龄时头部接受单剂量 5 Gy 伽马射线照射。测定了祖细胞增殖、分化和新生神经元的长期存活。与雄性小鼠的结果类似,EC-SOD 缺乏和辐射都会导致雌性小鼠成熟新生神经元的显着减少。 EC-SOD 缺乏会降低新生神经元的长期存活率,而辐射会降低祖细胞增殖。 EC-SOD 的过度表达纠正了 EC-SOD 缺乏和辐射的负面影响,并使 OE 小鼠新生神经元的产生正常化。 WT 小鼠中神经营养因子 BDNF 和 NTF3 的表达因辐射而显着降低,但 KO 和 OE 小鼠中的水平没有变化,尽管这两个组群的基线水平较低。就海马神经发生而言,EC-SOD 缺乏和辐射对进行研究的年龄的男性和女性具有相同的总体影响。
Altered levels of extracellular superoxide dismutase (EC-SOD) and cranial irradiation have been shown to affect hippocampal neurogenesis. However, previous studies were only conducted in male mice, and it was not clear if there was a difference between males and females. Therefore, female mice were studied and the results compared to those generated in male mice from an earlier study. Female wild type (WT), EC-SOD null (KO), and EC-SOD bi-genic mice with neuronal-specific expression of EC-SOD (OE) were subjected to a single dose of 5 Gy gamma rays to the head at 8 weeks of age. Progenitor cell proliferation, differentiation, and long-term survival of newborn neurons were determined. Similar to results from male mice, EC-SOD deficiency and irradiation both resulted in significant reductions in mature newborn neurons in female mice. EC-SOD deficiency reduced long-term survival of newborn neurons while irradiation reduced progenitor cell proliferation. Overexpression of EC-SOD corrected the negative impacts from EC-SOD deficiency and irradiation and normalized the production of newborn neurons in OE mice. Expression of neurotrophic factors, BDNF and NTF3, were significantly reduced by irradiation in WT mice, but the levels were not changed in KO and OE mice even though both cohorts started out with a lower baseline level. In terms of hippocampal neurogenesis, EC-SOD deficiency and irradiation have the same overall effects in males and females at the age the studies were conducted.
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