Winocur Gordon, Wojtowicz J Martin, Merkley Christina M, Tannock Ian F
Rotman Research Institute.
Department of Physiology, University of Toronto.
Behav Neurosci. 2016 Aug;130(4):428-36. doi: 10.1037/bne0000155. Epub 2016 Jun 23.
Clinical studies indicate that up to 70% of cancer patients who receive chemotherapy experience cognitive impairment. The present study investigated environmental enrichment as a protective factor against the adverse effects of anticancer drugs on cognitive and biological processes in an animal model. Adult rats were housed in group cages with environmental stimulation or in standard cages for 3 months, before receiving 3 weekly injections of methotrexate + 5-fluorouracil, or equal volumes of saline. Rats were then administered tests of learning and memory that are sensitive to hippocampal or frontal lobe dysfunction. The relationship between cognitive performance and hippocampal neurogenesis was examined through sensitive time-dependent measures of neuronal maturation. Chemotherapy-treated rats in the standard environment were impaired on tests of spatial memory, nonmatching-to-sample (NMTS) rule learning, and delayed-NMTS. Chemotherapy-treated rats in the enriched environment performed at or near normal levels. The performance of the chemotherapy groups on the hippocampus-sensitive, spatial memory and delayed-NMTS tests correlated with neurogenesis levels. The results show that environmental enrichment can reduce the risk of chemotherapy-induced cognitive impairment, in part by promoting neuronal differentiation and growth during cell maturation. As well, they point to the importance of lifestyle factors in treating or preventing adverse effects of anticancer drugs on cognitive function. (PsycINFO Database Record
临床研究表明,接受化疗的癌症患者中,高达70%会出现认知障碍。本研究在动物模型中探究了丰富环境作为一种保护因素,对抗癌药物对认知和生物过程的不良影响。成年大鼠被饲养在有环境刺激的群居笼中或标准笼中3个月,然后每周注射3次甲氨蝶呤+5-氟尿嘧啶,或等量的生理盐水。随后对大鼠进行对海马体或额叶功能障碍敏感的学习和记忆测试。通过对神经元成熟的敏感时间依赖性测量,研究了认知表现与海马体神经发生之间的关系。在标准环境中接受化疗的大鼠在空间记忆、非匹配样本(NMTS)规则学习和延迟NMTS测试中表现受损。在丰富环境中接受化疗的大鼠表现达到或接近正常水平。化疗组在对海马体敏感的空间记忆和延迟NMTS测试中的表现与神经发生水平相关。结果表明,丰富环境可以降低化疗引起的认知障碍风险,部分原因是在细胞成熟过程中促进神经元分化和生长。此外,它们还指出了生活方式因素在治疗或预防抗癌药物对认知功能的不良影响方面的重要性。(PsycINFO数据库记录)