Austin Christine, Smith Tanya M, Farahani Ramin M Z, Hinde Katie, Carter Elizabeth A, Lee Joonsup, Lay Peter A, Kennedy Brendan J, Sarrafpour Babak, Wright Rosalind J, Wright Robert O, Arora Manish
Senator Frank R. Lautenberg Environmental Health Sciences Laboratory, Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
Faculty of Dentistry, The University of Sydney, Sydney, New South Wales 2006, Australia.
Sci Rep. 2016 Jan 4;6:18802. doi: 10.1038/srep18802.
Early life stress can disrupt development and negatively impact long-term health trajectories. Reconstructing histories of early life exposure to external stressors is hampered by the absence of retrospective time-specific biomarkers. Defects in tooth enamel have been used to reconstruct stress but the methods used are subjective and do not identify the specific biological systems impacted by external stressors. Here we show that external physical and social stressors impart biochemical signatures in primate teeth that can be retrieved to objectively reconstruct the timing of early life developmental disruptions. Using teeth from captive macaques, we uncovered elemental imprints specific to disruptions of skeletal growth, including major disruptions in body weight trajectory and moderate to severe illnesses. Discrete increases in heat shock protein-70 expression in dentine coincided with elemental signatures, confirming that elemental signals were associated with activation of stress-related pathways. To overcome limitations of conventional light-microscopic analysis, we used high resolution Raman microspectral imaging to identify structural and compositional alterations in enamel and dentine that coincided with elemental signatures and with detailed medical and behavioural data. Integrating these objective biochemical markers with temporal mapping of teeth enables the retrospective study of early life developmental disruptions and their ensuing health sequelae.
早年生活压力会扰乱发育，并对长期健康轨迹产生负面影响。由于缺乏回顾性的特定时间生物标志物，重建早年暴露于外部应激源的历史受到阻碍。牙釉质缺陷已被用于重建压力，但所使用的方法主观，且无法识别受外部应激源影响的特定生物系统。在此，我们表明，外部物理和社会应激源会在灵长类动物牙齿中留下生化特征，这些特征可以被提取出来，以客观地重建早年发育中断的时间。利用圈养猕猴的牙齿，我们发现了与骨骼生长中断相关的元素印记，包括体重轨迹的重大中断以及中度至重度疾病。牙本质中热休克蛋白 -70 表达的离散增加与元素特征相吻合，证实元素信号与应激相关途径的激活有关。为了克服传统光学显微镜分析的局限性，我们使用高分辨率拉曼显微光谱成像来识别牙釉质和牙本质中的结构和成分变化，这些变化与元素特征以及详细的医学和行为数据相吻合。将这些客观的生化标志物与牙齿的时间图谱相结合，能够对早年发育中断及其随后的健康后果进行回顾性研究。
