Developmental exposure to cannabidiol (CBD) alters longevity and health span of zebrafish (Danio rerio)
Developmental exposure to cannabidiol (CBD) alters longevity and health span of zebrafish (Danio rerio)
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DOI：
10.1007/s11357-020-00182-4
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发表时间：
2020-03-27
期刊：
影响因子：
5.6
通讯作者：
Ashpole, Nicole M.
中科院分区：
文献类型：
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作者：
Pandelides, Zacharias;Thornton, Cammi;Ashpole, Nicole M.
含大麻素产品的消费量正在上升，即使在怀孕期间也是如此。不幸的是，发育性大麻二酚（CBD）暴露的长期，与年龄相关的后果在很大程度上仍然未知。这是一个关键的差距，因为建立了健康和疾病的发展起源（DOHaD）范式，强调压力，如药物暴露，在生命早期可以煽动分子和细胞的变化，最终导致不利的结果在以后的生活。因此，我们暴露斑马鱼（Danio rerio）不同浓度的CBD（0.02，0.1，0.5 μ M）在幼虫发育和评估老化的F0（暴露一代）和他们的F1后代30个月后。F0暴露于CBD显着增加了雌性鱼的存活率（类似于20%）并减少了雌性鱼的尺寸（湿重和长度）。虽然存活率增加，但与年龄相关的运动功能丧失不受影响，对生育力的影响因性别和剂量而异。用0.5 μ M CBD处理显著降低了雄性的精子浓度，但0.1 μ M增加了雌性的卵子产量。与其他模型系统相似，对照组老年斑马鱼表现出脊柱后凸增加以及肝脏中衰老和炎症（p16（ink4ab），tnf alpha，il1b，il6和ppar gamma）的表达标记增加。相对于年龄匹配的对照组，暴露于CBD以剂量依赖性方式显着降低了这些基因中几个的表达。CBD对大小，基因表达和繁殖的影响在F1代中没有重现，这表明对衰老的影响不是跨代的。总之，我们的研究结果表明，发育暴露于CBD会对斑马鱼的健康和寿命产生显着影响。
Consumption of cannabinoid-containing products is on the rise, even during pregnancy. Unfortunately, the long-term, age-related consequences of developmental cannabidiol (CBD) exposure remain largely unknown. This is a critical gap given the established Developmental Origins of Health and Disease (DOHaD) paradigm which emphasizes that stressors, like drug exposure, early in life can instigate molecular and cellular changes that ultimately lead to adverse outcomes later in life. Thus, we exposed zebrafish (Danio rerio) to varying concentrations of CBD (0.02, 0.1, 0.5 mu M) during larval development and assessed aging in both the F0 (exposed generation) and their F1 offspring 30 months later. F0 exposure to CBD significantly increased survival (similar to 20%) and reduced size (wet weight and length) of female fish. While survival was increased, the age-related loss of locomotor function was unaffected and the effects on fecundity varied by sex and dose. Treatment with 0.5 mu M CBD significantly reduced sperm concentration in males, but 0.1 mu M increased egg production in females. Similar to other model systems, control aged zebrafish exhibited increased kyphosis as well as increased expression markers of senescence, and inflammation (p16(ink4ab), tnf alpha, il1b, il6, and ppar gamma) in the liver. Exposure to CBD significantly reduced the expression of several of these genes in a dose-dependent manner relative to the age-matched controls. The effects of CBD on size, gene expression, and reproduction were not reproduced in the F1 generation, suggesting the influence on aging was not cross-generational. Together, our results demonstrate that developmental exposure to CBD causes significant effects on the health and longevity of zebrafish.