Han Haijun, Du Wenjuan, Zhou Bingrui, Zhang Wen, Xu Guoli, Niu Ruiyan, Sun Zilong
Shanxi Key Laboratory of Environmental Medicine, Shanxi Agricultural University, Taigu, Shanxi, China,
Biol Trace Elem Res. 2014 Apr;158(1):58-64. doi: 10.1007/s12011-014-9889-7. Epub 2014 Feb 4.
This study aimed to investigate the effects of long-term fluoride exposure on object recognition memory and mRNA expression of soluble N-ethylmaleimidesensitive fusion protein attachment protein receptors (SNARE) complex (synaptosome-associated protein of 25 kDa (SNAP-25), vesicle-associated membrane protein 2 (VAMP-2), and syntaxin 1A) in the hippocampus of male mice. Sixty sexually matured male Kunming mice were randomly divided into four groups: control group (given distilled water), low F group (25 mg/L NaF, corresponding to 11 mg/L F(-)), medium F group (50 mg/L NaF, corresponding to 22 mg/L F(-)), and high F group (100 mg/L NaF, corresponding to 45 mg/L F(-)). After 180 days, the spontaneous locomotor behavior and object recognition memory were detected by open field test and novel object recognition (NOR) test. Results showed that compared with the control group, frequency in each zone, total distance, and line crosses were significantly increased in low F and medium F groups, suggesting fluoride enhanced excitement of mice, while there were no marked changes in high F group. Twenty-four hours after training, a deficit of long-term memory (LTM) occurred only in high F group (P < 0.05), but there was no significant change of short-term memory (STM) 1.5 h later. The mRNA expression levels of SNAP-25, VAMP-2, and syntaxin 1A were detected by real-time quantitative RT-PCR, which revealed that the mRNA expression of VAMP-2 was significantly increased in medium F and high F groups (P < 0.01). Taken together, these results indicated that long-term fluoride administration can enhance the excitement of male mice, impair recognition memory, and upregulate VAMP-2 mRNA expression, which are involved in the adverse effects of fluoride on the object recognition memory of nervous system.
本研究旨在探讨长期氟暴露对雄性小鼠海马体中物体识别记忆以及可溶性N - 乙基马来酰亚胺敏感融合蛋白附着蛋白受体(SNARE)复合体(25 kDa突触体相关蛋白(SNAP - 25)、囊泡相关膜蛋白2(VAMP - 2)和 syntaxin 1A)mRNA表达的影响。将60只性成熟的雄性昆明小鼠随机分为四组:对照组(给予蒸馏水)、低氟组(25 mg/L NaF,相当于11 mg/L F(-))、中氟组(50 mg/L NaF,相当于22 mg/L F(-))和高氟组(100 mg/L NaF,相当于45 mg/L F(-))。180天后,通过旷场试验和新物体识别(NOR)试验检测自发运动行为和物体识别记忆。结果显示,与对照组相比,低氟组和中氟组各区域的频率、总距离和穿越次数均显著增加,表明氟增强了小鼠的兴奋性,而高氟组无明显变化。训练24小时后,仅高氟组出现长期记忆(LTM)缺陷(P < 0.05),但1.5小时后短期记忆(STM)无显著变化。通过实时定量RT - PCR检测SNAP - 25、VAMP - 2和syntaxin 1A的mRNA表达水平,结果显示中氟组和高氟组VAMP - 2的mRNA表达显著增加(P < 0.01)。综上所述,这些结果表明长期给予氟可增强雄性小鼠的兴奋性、损害识别记忆并上调VAMP - 2 mRNA表达,这些均与氟对神经系统物体识别记忆的不良影响有关。