Rider University, Department of Biology, 2083 Lawrenceville Road, Lawrenceville, NJ 08648, USA.
Rider University, Department of Biology, 2083 Lawrenceville Road, Lawrenceville, NJ 08648, USA.
Behav Brain Res. 2013 Jan 1;236(1):180-185. doi: 10.1016/j.bbr.2012.08.046. Epub 2012 Sep 4.
Cancer patients often suffer long-lasting affective and cognitive impairments as a result of chemotherapy treatment. Previous work in our lab has shown deficits in learning and memory and hippocampal cell proliferation in mice lasting up to 20 weeks following acute administration of thioTEPA. In this study, the effects of thioTEPA in conjunction with effects of chronic stress on depression-related behavior were examined in C57BL/6J mice, 12 weeks following thioTEPA administration. Chemotherapy-treated mice showed a diminished sucralose preference compared to controls that was further exacerbated after 2 weeks of daily restraint stress. This intensifying effect was not observed in the Porsolt forced swim test. Moreover, stress-induced corticosteroid responses were exaggerated in thioTEPA-treated mice. Cell proliferation in the dentate gyrus of the hippocampus was also impaired similarly by prior thioTEPA treatment and by daily restraint stress, with no additive effect. Results suggest that some depression-related impairments may be exacerbated by chemotherapy treatment through altered corticosteroid regulation.
癌症患者经常因化疗而遭受持久的情感和认知障碍。我们实验室之前的工作表明，在急性给予噻替派后，小鼠的学习和记忆以及海马细胞增殖缺陷可持续长达 20 周。在这项研究中，在噻替派给药后 12 周，检查了噻替派与慢性应激对 C57BL/6J 小鼠的抑郁相关行为的影响。与对照组相比，化疗处理的小鼠对蔗糖的偏好降低，而在每日束缚应激 2 周后，这种情况进一步恶化。在 Porsolt 强迫游泳试验中未观察到这种增强作用。此外，应激诱导的皮质酮反应在噻替派处理的小鼠中被夸大。先前的噻替派处理和每日束缚应激同样损害了海马齿状回的细胞增殖，没有相加作用。结果表明，一些与抑郁相关的损伤可能通过改变皮质酮调节而因化疗治疗而加剧。
