Integrative Immunology and Behavior Program, Department of Animal Sciences, College of ACES, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Brain Behav Immun. 2013 Aug;32:63-9. doi: 10.1016/j.bbi.2013.02.003. Epub 2013 Feb 26.
Geriatric depression is a costly health issue, but little is known about its physiological underpinnings. Systemic inflammation sensitizes the innate immune system of aged animals and humans, but it is unknown if chronic, low-grade infections affect the duration of depressive-like behaviors. In this report, we infected adult (4-6 months) and aged (20-24 months) Balb/c mice with an attenuated strain of Mycobacterium bovis, Bacillus Calmette-Guérin (BCG), to induce a chronic infection. We then measured depression-like behaviors that have construct, face and predictive validity for human inflammation-associated clinical depression. Exposure to BCG caused acute sickness responses in both adult and aged mice. However, sickness behavior was prolonged in aged mice, as assessed by both locomotor and rearing activity. Two measures of depression-like behavior, which were tests involving sucrose preference and tail suspension, both showed that adult mice displayed depression-like behaviors at one day and seven days after exposure to BCG. However, aged mice continued to express both of these depression-like behaviors at three weeks following infection. Infection with BCG caused an increase in tryptophan catabolism, as evidenced by a significant rise in the plasma kynurenine/tryptophan ratio that peaked at 7 days post-infection. In aged mice, greater tryptophan catabolism persisted longer and remained elevated at 21 days post-infection. This finding is consistent with the prolonged duration of depression-like behaviors in aged mice. These are the first data using a chronic infection model to establish that recovery from inflammation-induced depression-like behavior and tryptophan catabolism are prolonged in aged animals.
老年抑郁症是一个代价高昂的健康问题，但人们对其生理基础知之甚少。系统性炎症使老年动物和人类的固有免疫系统变得敏感，但尚不清楚慢性、低度感染是否会影响类似抑郁行为的持续时间。在本报告中，我们用减毒的牛分枝杆菌（BCG）感染成年（4-6 个月）和老年（20-24 个月）Balb/c 小鼠，以诱导慢性感染。然后，我们测量了具有构建、面部和预测人类炎症相关临床抑郁症有效性的类似抑郁行为。BCG 暴露在成年和老年小鼠中均引起急性疾病反应。然而，如通过运动和站立活动评估，疾病行为在老年小鼠中持续时间更长。两种类似抑郁行为的测量方法，即涉及蔗糖偏好和悬尾的测试，均表明成年小鼠在接触 BCG 后一天和七天表现出类似抑郁的行为。然而，感染后三周，老年小鼠仍继续表现出这两种类似抑郁的行为。BCG 感染导致色氨酸分解代谢增加，这表现在血浆犬尿氨酸/色氨酸比值显著升高，在感染后 7 天达到峰值。在老年小鼠中，更大的色氨酸分解代谢持续时间更长，在感染后 21 天仍保持升高。这一发现与老年小鼠类似抑郁行为持续时间延长一致。这些是首次使用慢性感染模型的数据，证明了炎症引起的类似抑郁行为和色氨酸分解代谢的恢复在老年动物中是延长的。
