中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (11): 2497-2503.doi: 10.4103/1673-5374.338999

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

丰富环境减轻脑卒中海马炎症反应及改善认知功能

  

  • 出版日期:2022-11-15 发布日期:2022-04-22
  • 基金资助:
    国家自然科学基金项目(82072533),中国博士后科研基金项目(2017M621675),江苏省人畜共患病重点实验室沪新基金项目(HX2003);扬州市科技发展计划项目(YZ2020201)

An enriched environment reduces hippocampal inflammatory response and improves cognitive function in a mouse model of stroke

Hong-Yu Zhou1, #, Ya-Ping Huai2, #, Xing Jin1, Ping Yan3, Xiao-Jia Tang1, Jun-Ya Wang1, Nan Shi3, Meng Niu4, Zhao-Xiang Meng1, *, Xin Wang1, *   

  1. 1Department of Rehabilitation Medicine, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University (Clinical Medical College, Yangzhou University), Yangzhou, Jiangsu Province, China; 2Department of Rehabilitation Medicine, Shenzhen Longhua District Central Hospital, Shenzhen, Guangdong Province, China; 3School of Nursing, Yangzhou University, Yangzhou, Jiangsu Province, China; 4Dalian Medical University, Dalian, Liaoning Province, China
  • Online:2022-11-15 Published:2022-04-22
  • Contact: Xin Wang, PhD, wx000805qm@yeah.net; Zhao-Xiang Meng, PhD, yzmzx001@163.com.
  • Supported by:
    This study was financially supported by the National Natural Science Foundation of China, No. 82072533, the China Postdoctoral Science Foundation, No. 2017M621675, Huxin Foundation of Jiangsu Key Laboratory of Zoonosis of China, No. HX2003; and Yangzhou Science and Technology Development Plan Project of China, No. YZ2020201 (all to XW).

摘要:

丰富环境是一种以感觉、运动和社交刺激为主体的行为干预疗法,已被用于多种神经系统疾病的基础和临床研究中。实验以光栓塞法建立脑卒中模型小鼠,24h后起在标准环境、丰富环境和孤养环境中连续饲养小鼠4周。结果发现,与标准环境饲养的小鼠相比,丰富环境饲养的小鼠的认知功能有所改善,海马CA1区病理损伤明显减轻,炎症相关因子肿瘤坏死因子受体相关分子6、核因子κBp65、白细胞介素6 和肿瘤坏死因子α蛋白以及肿瘤坏死因子受体相关分子6 mRNA表达下降,而miR-146a-5p表达增加。同时与标准环境饲养的小鼠相比,孤养环境饲养的小鼠上述指标的变化相反。表明不同居住环境可对脑卒中小鼠海马炎症反应及认知功能产生影响,且丰富环境通过与上调miR-146a-5p水平,降低神经炎症反应而改善脑卒中后认知功能。

https://orcid.org/0000-0003-1961-9615 (Xin Wang); https://orcid.org/0000-0001-9624-2829 (Zhao-Xing Meng)

关键词: 丰富环境, 孤养环境, miR-146a-5p, 肿瘤坏死因子受体相关分子6, 核因子κBp65, 神经炎症, 脑卒中, 光栓塞, 认知功能

Abstract: An enriched environment is used as a behavioral intervention therapy that applies sensory, motor, and social stimulation, and has been used in basic and clinical research of various neurological diseases. In this study, we established mouse models of photothrombotic stroke and, 24 hours later, raised them in a standard, enriched, or isolated environment for 4 weeks. Compared with the mice raised in a standard environment, the cognitive function of mice raised in an enriched environment was better and the pathological damage in the hippocampal CA1 region was remarkably alleviated. Furthermore, protein expression levels of tumor necrosis factor receptor-associated factor 6, nuclear factor κB p65, interleukin-6, and tumor necrosis factor α, and the mRNA expression level of tumor necrosis factor receptor-associated factor 6 were greatly lower, while the expression level of miR-146a-5p was higher. Compared with the mice raised in a standard environment, changes in these indices in mice raised in an isolated environment were opposite to mice raised in an enriched environment. These findings suggest that different living environments affect the hippocampal inflammatory response and cognitive function in a mouse model of stroke. An enriched environment can improve cognitive function following stroke through up-regulation of miR-146a-5p expression and a reduction in the inflammatory response.

Key words: cognitive function, enriched environment, isolated environment, miR-146a-5p, neuroinflammation, nuclear factor κB p65, photothrombotic model, stroke, tumor necrosis factor receptor-associated factor 6