王永生,王明明.氚对神经细胞迁移相关因子表达及空间学习记忆能力的影响[J].中华放射医学与防护杂志,2019,39(12):887-892
氚对神经细胞迁移相关因子表达及空间学习记忆能力的影响
Expression of neuronal migration-related factors and the spatial learning and memory of rats prenatally exposed to tritiated water
投稿时间:2019-08-02  
DOI:10.3760/cma.j.issn.0254-5098.2019.12.002
中文关键词:  神经细胞  氚水  神经元迁移相关因子  空间学习与记忆能力
英文关键词:Neuronal cell  Tritiated water  Neuronal migration related factor  Spatial learning and memory
基金项目:安徽省自然科学基金(1208085MH162)
作者单位E-mail
王永生 东南大学附属中大医院核医学科, 南京 210000  
王明明 安徽医学高等专科学校附属医院放射卫生科, 合肥 230001 wmgene@163.com 
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中文摘要:
      目的 探讨氚水(HTO)对大鼠海马神经细胞迁移相关因子表达及空间学习记忆能力的影响。方法 取24 h内新生鼠脑海马细胞培养,培养第7天以0、3.7×102、3.7×103、3.7×104、3.7×105、3.7×106 Bq/ml终浓度氚水培养细胞24 h;Western blot法、RT-PCR法分别检测各浓度氚水处理后的神经细胞骨架蛋白(F-肌动蛋白、α-微管蛋白、tau蛋白及MAP2蛋白)、脑源性神经细胞营养因子(BDNF)及Reelin mRNA的表达情况。取妊娠14 d孕鼠16只,采用随机数表法分两组,每组8只,实验组单次注射3.7×106 Bq/g (体重)氚水,对照组注射等量体积生理盐水,Morris水迷宫法观察出生后两组大鼠的空间学习能力。结果 3.7×102、3.7×103、3.7×104、3.7×105、3.7×106 Bq/ml终浓度氚水处理后的神经细胞中,F-肌动蛋白(t=8.898~25.749,P<0.05)、α-微管蛋白(t=3.261~7.900,P<0.05)、tau (t=2.274~5.003,P<0.05)、MAP2(t=2.274~5.003,P<0.05)、BDNF mRNA (t=3.580~19.792,P<0.05)、Reelin mRNA (t=3.240~39.692,P<0.05)表达水平均低于0 Bq/ml浓度并随氚水浓度的升高表达量呈递减趋势。Morris水迷宫结果显示,与对照组相比,实验组大鼠逃避潜伏期延长(t=-2.563,P<0.05),目标象限穿行次数减少、停留时间缩短(t=3.214、3.874,P<0.05)。结论 HTO辐射对大鼠神经元迁移相关因子表达和空间学习有影响,这可能有助于了解放射性脑损伤的机制。
英文摘要:
      Objective To study the expression of neuronal migration-related factors and spatial learning and memory of rats exposed to tritiated water (HTO). Methods Hippocampal neural cells from newborn Sprague-Dawley(SD) rats at postnatal 24 h were primarily cultured in DMEM/F12 medium with 20% of fetal bovine serum for 6 days, followed by subjection to tritiated water(HTO) at concentrations of 3.7×102, 3.7×103, 3.7×104, 3.7×105, 3.7×106 Bq/ml for 24 h, respectively. Western blot and RT-qPCR were used to determine the expression levels of F-actin, α-tubulin, tau, AP2, BDNF mRNA and Reelin mRNA. 16 pregnant SD rats at embryonic (E) day 14 were randomly divided into the tested and control groups (8 rats/each group). The tested rats were injected with body fluid of HTO (3.7×106 Bq/g) intraperitoneally, while the saline as the control. Morris water maze (MWM) was employed for the spatial learning and memory of rats. Results Compared to the control cells, HTO caused a significant downregulation of expressions of cytoskeletal proteins[F-actin (t=8.898-19.896, P<0.05), α-tubulin (t=3.261-7.900, P<0.05), tau (t=2.274-5.003, P<0.05), and MAP2 (t=2.274-5.003, P<0.05)] and mRNA of BDNF(t=3.580-19.792, P<0.05) and Reelin (t=3.240-39.692, P<0.05) in the tested neural cells in a dose-dependent manner. In addition, the escape latency of irradiated offsprings was significantly prolonged (t=-2.563, P<0.05), the time for offsprings to cross through target quadrant was markedly reduced (t=3.214, P<0.05), and the swimming time in the platform quadrant of irradiated offsprings were obviously shortened (t=3.874, P<0.05) in the MWM trial. Conclusions The results indicate that HTO irradiation in utero downregulates the expressions of neuron migration-related factors and induces brain dysfunction, which may shed a light on a mechanism of the radiation-induced brain impairment.
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