Neural Regeneration Research ›› 2020, Vol. 15 ›› Issue (12): 2327-2334.doi: 10.4103/1673-5374.285005

Previous Articles     Next Articles

Enriched environment enhances histone acetylation of NMDA receptor in the hippocampus and improves cognitive dysfunction in aged mice

Xin Wang 1, 2 , Zhao-Xiang Meng 2 , Ying-Zhu Chen 2 , Yu-Ping Li 2 , Hong-Yu Zhou 2 , Man Yang 3 , Ting-Ting Zhao 3 , Yu-Lai Gong 4 , Yi Wu 1, Tao Liu 5   

  1. 1 Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, China
    2 Department of Rehabilitation, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China
    3 Department of Rehabilitation, First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning Province, China
    4 Department of Rehabilitation Medicine, Sichuan Provincial Rehabilitation Hospital Affiliated to Chengdu University of TCM, Chengdu, Sichuan Province, China
    5 South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China
  • Online:2020-12-15 Published:2020-08-05
  • Contact: Yi Wu, MD, PhD, wuyi@fudan.edu.cn; Tao Liu, PhD, lt045021@gzucm.edu.cn.
  • Supported by:
    The study was supported by the National Natural Science Foundation of China, Nos. 81672242, 81972141 (both to YW); the China Postdoctoral Science Fund, No. 2017M621675 (to XW); the Natural Science Foundation of Jiangsu Province of China, No. BK20171280 (to XW); the Six One Project of Scientific Research Project for High-Level Health Talents of Jiangsu Province of China, Nos. LGY2017028, LGY2018027 (to XW); the Key Young Medical Talents Project of Jiangsu Province, No. QNRC2016339 (to XW); the Yangzhou’s 13 th Five-Year Plan for “Ke Jiao Qiang Wei” of China, No. ZDRC65 (to XW); the Key Project of Shanghai Science and Technology on Biomedicine of China, No. 17411953900 (to YW).

PDF

135

Abstract: The mechanisms of age-associated memory impairment may be associated with glutamate receptor function and chromatin modification. To observe the effect of an enriched environment on the cognitive function of mice with age-associated memory impairment, 3-month- old C57BL/6 male mice (“young” mice) were raised in a standard environment, while 24-month-old C57BL/6 male mice with memory impairment (“age-associated memory impairment” mice) were raised in either a standard environment or an enriched environment. The enriched environment included a variety of stimuli involving movement and sensation. A water maze test was then used to measure cog- nitive function in the mice. Furthermore, quantitative real-time polymerase chain reaction and western blot assays were used to detect right hippocampal GluN2B mRNA as well as protein expression of GluN2B and CREB binding protein in all mice. In addition, chromatin immunoprecipitation was used to measure the extent of histone acetylation of the hippocampal GluN2B gene promoters. Compared with the young mice, the water maze performance of age-associated memory impairment mice in the standard environment was significantly decreased. In addition, there were significantly lower levels of total histone acetylation and expression of CREB binding protein in the hippocampus of age-associated memory impairment mice in the standard environment compared with the young mice. There were also significantly lower levels of histone acetylation, protein expression, and mRNA expression of GluN2B in the hippocampus of these mice. In contrast, in the age-associated memory impairment mice with the enriched environment intervention, the water maze performance and molecular biological indexes were significantly improved. These data confirm that an enriched environment can improve cognitive dys- function in age-associated memory impairment mice, and suggest that the mechanisms may be related to the increased expression of CREB binding protein and the increased degree of total histone acetylation in the hippocampus of age-associated memory impairment mice, which may cause the increase of histone acetylation of GluN2B gene promoter and the enhancement of GluN2B mRNA transcription and protein expression in hippocampus. The animal experiment was approved by the Animal Ethics Committee of Yangzhou University, China (approval No. 20170312001) in March 2017.

Key words: brain, central nervous system, factor, in vitro, model, mice, recovery, regenerations protein