中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (6): 1062-1067.doi: 10.4103/1673-5374.300460

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

虾青素可通过上调海马突触蛋白表达延缓病理性脑老化

  

  • 出版日期:2021-06-15 发布日期:2020-12-31
  • 基金资助:
    中国国际自然科学基金项目（8177051488）

Astaxanthin alleviates pathological brain aging through the upregulation of hippocampal synaptic proteins

Ning Liu1, 2, Liang Zeng3, Yi-Ming Zhang1, Wang Pan4, Hong Lai1, *   

  1. 1 Department of Human Anatomy, College of Basic Medicine, China Medical University, Shenyang, Liaoning Province, China;  2 Department of Radiology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning Province, China;  3 Department of Human Anatomy, College of Basic Medicine, Shenyang Medical College, Shenyang, Liaoning Province, China;  4 Department of Neurobiology of Jinzhou Medical University, Jinzhou, Liaoning Province, China
  • Online:2021-06-15 Published:2020-12-31
  • Contact: Hong Lai, MD, hlai@cmu.edu.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, No. 8177051488 (to HL).

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摘要：

虾青素可改善多种病理情况下的氧化应激情况，而氧化应激是脑衰老的主要原因；因而推测虾青素可能对脑老化发挥治疗作用，为验证这一假设，并探索其机制，实验通过连续6次对侧脑室注射Aβ25-35（5μM，3μL/ d），隔天1次，构建了脑老化ICR小鼠模型，并在注射Aβ25-35 3d后，连续30d灌胃虾青素（0.1 mL/d，10 mg/kg）。结果表明，虾青素治疗可明显减少小鼠在Morris水迷宫中潜伏期，增加穿越目标平台的次数，增加海马组织中脑源性神经营养因子、突触素、Sirtuin 1以及过氧化物酶体增殖物激活受体γ辅激活因子1α的表达；而接受虾青素治疗后连续7d腹腔注射Sirtuin 1抑制剂烟酰胺（500μM/d）可抑制上述作用。表明虾青素可通过Sirtuin 1/过氧化物酶体增殖物激活受体γ辅激活因子1α信号通路调节小鼠海马突触蛋白的表达，从而改善衰老小鼠的学习、认知和记忆能力。实验于2019年1月15日经中国医科大学动物伦理委员会批准，批准号CMU2019294。

https://orcid.org/0000-0002-2748-5947 (Ning Liu); 

https://orcid.org/0000-0002-2889-8911 (Hong Lai)

关键词: 脑老化, 衰老, 海马, 氧化应激, 因子, 通路, 突触, 认知, 记忆, 学习

Abstract: Oxidative stress is currently considered to be the main cause of brain aging. Astaxanthin can improve oxidative stress under multiple pathological conditions. It is therefore hypothesized that astaxanthin might have therapeutic effects on brain aging. To validate this hypothesis and investigate the underlying mechanisms, a mouse model of brain aging was established by injecting amyloid beta (Aβ)25–35 (5 μM, 
3 μL/injection, six injections given every other day) into the right lateral ventricle. After 3 days of Aβ25–35 injections, the mouse models were intragastrically administered astaxanthin (0.1 mL/d, 10 mg/kg) for 30 successive days. Astaxanthin greatly reduced the latency to find the platform in the Morris water maze, increased the number of crossings of the target platform, and increased the expression of brain-derived neurotrophic factor, synaptophysin, sirtuin 1, and peroxisome proliferator-activated receptor-γ coactivator 1α. Intraperitoneal injection of the sirtuin 1 inhibitor nicotinamide (500 μM/d) for 7 successive days after astaxanthin intervention inhibited these phenomena. These findings suggest that astaxanthin can regulate the expression of synaptic proteins in mouse hippocampus through the sirtuin 1/peroxisome proliferator-activated receptor-γ coactivator 1α signaling pathway, which leads to improvements in the learning, cognitive, and memory abilities of mice. The study was approved by the Animal Ethics Committee, China Medical University, China (approval No. CMU2019294) on January 15, 2019.  

Key words: brain aging, cognitive, factor, hippocampus, learning, memory, oxidative stress, pathways, synapse