Department of Psychology, College of Liberal Arts, Texas A&M University, College Station, TX, 77843-4235, USA.
Behav Genet. 2010 Mar;40(2):233-49. doi: 10.1007/s10519-010-9333-5. Epub 2010 Feb 5.
Previous studies have established a link between adverse early life events and subsequent disease vulnerability. The present study assessed the long-term effects of neonatal maternal separation on the response to Theiler's murine encephalomyelitis virus infection, a model of multiple sclerosis. Balb/cJ mouse pups were separated from their dam for 180-min/day (180-min MS), 15-min/day (15-min MS), or left undisturbed from postnatal days 2-14. During adolescence, mice were infected with Theiler's virus and sacrificed at days 14, 21, or 35 post-infection. Prolonged 180-min MS increased viral load and delayed viral clearance in the spinal cords of males and females, whereas brief 15-min MS increased the rate of viral clearance in females. The 15-min and 180-min MS mice exhibited blunted corticosterone responses during infection, suggesting that reduced HPA sensitivity may have altered the immune response to infection. These findings demonstrate that early life events alter vulnerability to CNS infection later in life. Therefore, this model could be used to study gene-environment interactions that contribute to individual differences in susceptibility to infectious and autoimmune diseases of the CNS.
先前的研究已经证实，不良的早期生活事件与随后的疾病易感性之间存在关联。本研究评估了新生期母体分离对 T 细胞性脑脊髓炎病毒感染（多发性硬化症模型）反应的长期影响。Balb/cJ 幼鼠从出生后第 2 天到第 14 天，每天被分离 180 分钟（180 分钟 MS）、15 分钟（15 分钟 MS）或不受干扰。在青春期，将小鼠感染 T 细胞性脑脊髓炎病毒，并在感染后第 14、21 或 35 天处死。长时间 180 分钟 MS 增加了雄性和雌性脊髓中的病毒载量并延迟了病毒清除，而短暂的 15 分钟 MS 增加了雌性的病毒清除率。15 分钟和 180 分钟 MS 小鼠在感染期间皮质酮反应减弱，这表明 HPA 敏感性降低可能改变了对感染的免疫反应。这些发现表明，早期生活事件会改变一生中对中枢神经系统感染的易感性。因此，该模型可用于研究导致中枢神经系统感染和自身免疫性疾病易感性个体差异的基因-环境相互作用。
