Department of Physiology and Pharmacology, School of Medicine, Alborz University of Medical Sciences, Alborz, Iran.
Salari Institute of Cognitive and Behavioral Disorders (SICBD), Alborz, Iran; Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Neuropharmacology. 2019 Oct;157:107685. doi: 10.1016/j.neuropharm.2019.107685. Epub 2019 Jun 25.
Emerging evidence indicates that gut microbiota interacts with immune and nervous systems in the host and plays a critical role in the pathogenesis of multiple sclerosis (MS) and many psychiatric disorders such as depression and anxiety. The aim of this study was to explore the influence of gut bacterial depletion from early adolescence on adult immunological and neurobehavioral responses in mice with experimental-autoimmune-encephalomyelitis (EAE). We used an animal model of gut microbiota depletion induced by antibiotics from weaning to adulthood to assess clinical signs, cognitive function and depression-and anxiety-related symptoms in non-EAE and EAE-induced mice. We measured levels of interferon (IFN)-γ, interleukin (IL)-17A and IL-10 in serum, and BDNF, IL-1β and tumor necrosis factor (TNF)-α) in the hippocampus. Antibiotic-treated mice displayed a significant delay in the onset of clinical symptoms of EAE. However, a higher severity of EAE was found between days 19-22 post-immunization in antibiotics-treated mice, while a reduction in the clinical signs of MS was observed at days 24-25 post-immunization. Antibiotic administration decreased IFN-γ and IL-17A levels and increased IL-10 in serum of EAE-induced mice. Antibiotic treatment significantly decreased hippocampal BDNF and enhanced learning and memory impairments in EAE-induced mice. However, no significant changes were found in non-EAE mice. Non-EAE and EAE mice treated with antibiotics exhibited increased anxiety-related behaviors, whereas depression-related symptoms and increased hippocampal TNF-α and IL-1β were only observed in EAE-induced mice treated with antibiotics. This study supports the view that depletion of gut microbiota by antibiotics from weaning profoundly impacts adult immunological and neurobehavioral responses.
新出现的证据表明，肠道微生物群与宿主的免疫和神经系统相互作用，在多发性硬化症 (MS) 和许多精神疾病（如抑郁和焦虑）的发病机制中发挥着关键作用。本研究旨在探索从青春期早期开始肠道细菌耗竭对实验性自身免疫性脑脊髓炎 (EAE) 小鼠成年免疫和神经行为反应的影响。我们使用抗生素从断奶到成年诱导的肠道微生物群耗竭动物模型来评估非 EAE 和 EAE 诱导的小鼠的临床症状、认知功能以及抑郁和焦虑相关症状。我们测量了血清中干扰素 (IFN)-γ、白细胞介素 (IL)-17A 和 IL-10 的水平，以及海马体中的脑源性神经营养因子 (BDNF)、IL-1β 和肿瘤坏死因子 (TNF)-α。抗生素处理的小鼠出现 EAE 临床症状的时间明显延迟。然而，在免疫后第 19-22 天，抗生素处理的小鼠中观察到 EAE 的严重程度更高，而在免疫后第 24-25 天观察到 MS 临床症状的减少。抗生素给药降低了 EAE 诱导小鼠血清中 IFN-γ 和 IL-17A 的水平，并增加了 IL-10。抗生素处理显著降低了 EAE 诱导小鼠海马体中的 BDNF，并增强了学习和记忆障碍。然而，在非 EAE 小鼠中未发现显著变化。非 EAE 和 EAE 小鼠用抗生素处理后表现出焦虑相关行为增加，而 EAE 诱导的用抗生素处理的小鼠仅表现出抑郁相关症状和海马体 TNF-α 和 IL-1β 增加。本研究支持这样一种观点，即从断奶开始用抗生素耗竭肠道微生物群会严重影响成年免疫和神经行为反应。
