中国神经再生研究(英文版) ›› 2016, Vol. 11 ›› Issue (10): 1617-1624.doi: 10.4103/1673-5374.193241

• 原著:退行性病与再生 • 上一篇    下一篇

激活β2肾上腺素受体能促进阿尔茨海默病小鼠的神经发生

  

  • 收稿日期:2016-09-06 出版日期:2016-10-31 发布日期:2016-10-31
  • 基金资助:
    江苏省自然科学基金项目(bk20150163);中央高校基基础科研基金(jusrp11567)

Beta 2-adrenergic receptor activation enhances neurogenesis in Alzheimer’s disease mice

Gao-shang Chai, Yang-yang Wang, Amina Yasheng, Peng Zhao*   

  1. Department of Basic Medicine, Wuxi Medical School, Jiangnan University, Wuxi, Jiangsu Province, China
  • Received:2016-09-06 Online:2016-10-31 Published:2016-10-31
  • Contact: Peng Zhao, Ph.D., M.D., chaigaoshang@jiangnan.edu.cn or Zhaopeng336@163.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 81601121, 31500968; the Natural Science Foundation of Jiangsu Province of China, No. BK20150163; the Fundamental Research Fund for the Central Universities of China, No. JUSRP11567.

摘要:

海马神经发生障碍是阿尔茨海默病早期病理改变之一,促进神经发生已成为防治阿尔茨海默病的新策略。近年的研究发现新鲜环境刺激能够通过β2肾上腺素受体信号途径降低由β淀粉样蛋白导致的认知障碍。基于此,我们提出激活β2肾上腺素受体能够促进神经发生,改善阿尔茨海默病认知障碍的假设。实验方案设计我们将β2肾上腺素受体激动剂-克伦特罗2 mg/kg腹腔注射于阿尔茨海默病APP/PS1转基因小鼠,发现激活β2肾上腺素受体能促进APP/PS1转基因小鼠海马神经发生,增加海马神经元树突和树突棘密度,同时伴有突触后密度蛋白95和突触素表达上调,改善其记忆障碍。此外,实验还发现激活β2肾上腺素受体对小鼠脑淀粉样斑块生成具有抑制作用,其机制与降低APP Thr668位点磷酸化有关。结果证实,激活β2肾上腺素受体能够促进APP/PS1小鼠神经发生,从而产生了改善认知障碍的作用。

orcid: 0000-0002-1943-3717 (Gao-shang Chai)

关键词: 阿尔茨海默病, β2-肾上腺素受体, β淀粉样蛋白, 神经发生, 克伦特罗, APP/PS1转基因鼠, 记忆, 树突棘, 突触蛋白1, 突触素, 突触后密度蛋白95

Abstract: Impaired hippocampal neurogenesis is one of the early pathological features of Alzheimer’s disease. Enhancing adult hippocampal neurogenesis has been pursued as a potential therapeutic strategy for Alzheimer’s disease. Recent studies have demonstrated that environmental novelty activates β2-adrenergic signaling and prevents the memory impairment induced by amyloid-β oligomers. Here, we hypothesized that β2-adrenoceptor activation would enhance neurogenesis and ameliorate memory defcits in Alzheimer’s disease. To test this hypothesis, we investigated the e?ects and mechanisms of action of β2-adrenoceptor activation on neurogenesis and memory in amyloid precursor protein/presenilin 1 (APP/PS1) mice using the agonist clenbuterol (intraperitoneal injection, 2 mg/kg). We found that β2-adrenoceptor activation enhanced hippocampal neurogenesis, ameliorated memory defcits, and increased dendritic branching and the density of dendritic spines. Tese e?ects were associated with the upregulation of postsynaptic density 95, synapsin 1 and synaptophysin in APP/PS1 mice. Furthermore, β2-adrenoceptor activation decreased cerebral amyloid plaques by decreasing APP phosphorylation at Tr668. Tese fndings suggest that β2-adrenoceptor activation enhances neurogenesis and ameliorates memory defcits in APP/PS1 mice.

Key words: nerve regeneration, Alzheimer’s disease, β2-adrenoceptors, amyloid β, neurogenesis, clenbuterol, APP/PS1 mice, memory, dendritic spine, synapsin 1, synaptophysin, postsynaptic density 95, neural regeneration