Sela Hagit, Cohen Hagit, Karpas Zeev, Zeiri Yehuda
Biomedical Engineering, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel.
Beer-Sheva Mental Health Center, The State of Israel Ministry of Health, Anxiety and Stress Research Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Metallomics. 2017 Mar 22;9(3):323-333. doi: 10.1039/c6mt00207b.
Emerging evidence suggests that zinc (Zn) deficiency is associated with depression and anxiety in both human and animal studies. The present study sought to assess whether there is an association between the magnitude of behavioral responses to stress and patterns of Zn distribution. The work has focused on one case study, the association between an animal model of posttraumatic stress disorder (PTSD) and the Zn distribution in the rat hippocampus. Behaviors were assessed with the elevated plus-maze and acoustic startle response tests 7 days later. Preset cut-off criteria classified exposed animals according to their individual behavioral responses. To further characterize the distribution of Zn that occurs in the hippocampus 8 days after the exposure, laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) imaging was used. It has been found that Zn distribution in the dentate gyrus (DG) sub-region in the hippocampus is clearly more widely spread for rats that belong to the extreme behavioral response (EBR) group as compared to the control group. Comparison of the Zn concentration changes in the cornu ammonis 1 (CA1) and the DG sub-regions of the hippocampus shows that the concentration changes are statistically significantly higher in the EBR rats compared to the rats in the control and minimal behavioral response (MBR) groups. In order to understand the mechanism of stress-induced hippocampal Zn dyshomeostasis, relative quantitative analyses of metallothionein (MT), B-cell lymphoma 2 (Bcl-2) and caspase 3 immunoreactivity were performed. Significant differences in the number of caspase-ir and Bcl-2 cells were found in the hippocampal DG sub-region between the EBR group and the control and MBR groups. The results of this study demonstrate a statistically significant association between the degree of behavioral disruption resulting from stress exposure and the patterns of Zn distribution and concentration changes in the various hippocampal regions. Taken together, these findings indicate that Zn distribution patterns play an active role in the neurobiological response to predator scent stress.
新出现的证据表明，在人类和动物研究中，锌（Zn）缺乏与抑郁和焦虑有关。本研究旨在评估应激行为反应的程度与锌分布模式之间是否存在关联。这项工作聚焦于一个案例研究，即创伤后应激障碍（PTSD）动物模型与大鼠海马体中锌分布之间的关联。7天后，通过高架十字迷宫和听觉惊吓反应测试对行为进行评估。预设的截断标准根据暴露动物的个体行为反应对其进行分类。为了进一步表征暴露8天后海马体中锌的分布情况，使用了激光烧蚀-电感耦合等离子体质谱（LA-ICP-MS）成像技术。研究发现，与对照组相比，属于极端行为反应（EBR）组的大鼠海马齿状回（DG）亚区域的锌分布明显更广泛。海马体角回1（CA1）和DG亚区域锌浓度变化的比较表明，与对照组和最小行为反应（MBR）组的大鼠相比，EBR大鼠的浓度变化在统计学上显著更高。为了了解应激诱导的海马体锌稳态失调的机制，对金属硫蛋白（MT）、B细胞淋巴瘤2（Bcl-2）和半胱天冬酶3免疫反应性进行了相对定量分析。在EBR组与对照组和MBR组之间的海马DG亚区域，发现半胱天冬酶免疫反应细胞和Bcl-2细胞数量存在显著差异。本研究结果表明，应激暴露导致的行为破坏程度与各海马区域锌分布和浓度变化模式之间存在统计学上的显著关联。综上所述，这些发现表明锌分布模式在对捕食者气味应激的神经生物学反应中发挥着积极作用。
