University of Crete, Department of Biology, P.O. Box 2208, GR-70013 Heraklion, Crete, Greece.
University of Crete, Department of Biology, P.O. Box 2208, GR-70013 Heraklion, Crete, Greece.
Prog Neuropsychopharmacol Biol Psychiatry. 2015 Jul 3;60:121-31. doi: 10.1016/j.pnpbp.2015.02.014. Epub 2015 Mar 5.
The main objectives of this study were to investigate the dynamics of the cortisol stress response and the underlying molecular regulation in adult zebrafish exposed to acute and long-term stressors that differed in nature, duration and relative intensity. Fish showed a very rapid and prolonged increase in trunk cortisol concentrations, starting at around 15min and returning to basal levels at around 2h following exposure to acute stressors. In addition, acute stress affected significantly brain mRNA expression levels of several genes (corticotropin-releasing factor, crf; pro-opiomelanocortin, pomc; glucocorticoid receptor, gr; MR/GR ratio; prolactin, prl; hypocretin/orexin, hcrt; brain-derived neurotrophic factor, bdnf; c-fos). Exposure of fish to unpredictable relatively low-grade environmental and husbandry stressors (SP-1) did not affect the overall behaviour of fish, as well as trunk cortisol concentrations. Fish exposed to relatively higher-grade long-term stressors (SP-2) showed elevated cortisol levels as well as significant changes in most of gene transcripts. In particular, fish exposed to SP-2 showed statistically significant upregulation in brain gr, mr, prl and hcrt compared to SP-1 and control individuals. The highest mean values of bdnf transcripts were found in SP-2 exposed zebrafish and the lowest in control fish, while an approximately 5 to 6-fold upregulation was observed in c-fos mean relative mRNA levels of long-term stress-exposed fish, regardless of stressor intensity, compared to control zebrafish. In conclusion, we developed realistic acute and unpredictable long-term stress protocols, based on husbandry and environmental stressors and physical, chemical, mechanical and social stimuli that fish may experience either in nature or under intensive rearing conditions.
本研究的主要目的是研究暴露于性质、持续时间和相对强度不同的急性和长期应激源的成年斑马鱼皮质醇应激反应的动力学及其潜在的分子调节。鱼在暴露于急性应激源后约 15 分钟开始，2 小时左右恢复到基础水平，其躯干皮质醇浓度迅速而持久地增加。此外，急性应激显著影响了几种基因（促肾上腺皮质释放因子，CRF；促阿黑皮素原，POMC；糖皮质激素受体，GR；MR/GR 比值；催乳素，PRL；食欲素/下丘脑分泌素，Hcrt；脑源性神经营养因子，BDNF；c-fos）的脑 mRNA 表达水平。鱼暴露于不可预测的相对低等级环境和养殖应激源（SP-1）不会影响鱼的整体行为以及躯干皮质醇浓度。暴露于相对较高等级的长期应激源（SP-2）的鱼显示皮质醇水平升高，以及大多数基因转录物的显著变化。特别是，与 SP-1 和对照个体相比，暴露于 SP-2 的鱼的大脑 GR、MR、PRL 和 Hcrt 基因转录物表达显著上调。暴露于 SP-2 的斑马鱼的 BDNF 转录物的平均水平最高，而对照鱼的最低，而无论应激源强度如何，长期应激暴露的鱼的 c-fos 平均相对 mRNA 水平约上调 5 到 6 倍。总之，我们根据养殖和环境应激源以及鱼在自然或集约化养殖条件下可能经历的物理、化学、机械和社会刺激，制定了现实的急性和不可预测的长期应激方案。
