中国神经再生研究(英文版) ›› 2017, Vol. 12 ›› Issue (11): 1832-1842.doi: 10.4103/1673-5374.219044

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

Akt/mTOR 信号通路活化:脓毒症海马神经元长期丢失的潜在反应

  

  • 收稿日期:2017-09-21 出版日期:2017-11-15 发布日期:2017-11-15
  • 基金资助:
    中国国家自然科学基金项目(81301659, 81401077

Activation of the Akt/mTOR signaling pathway: a potential response to long-term neuronal loss in the hippocampus after sepsis

Jia-nan Guo, Lin-yu Tian, Wen-yu Liu, Jie Mu, Dong Zhou   

  1. Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
  • Received:2017-09-21 Online:2017-11-15 Published:2017-11-15
  • Contact: Dong Zhou, M.D. or Lin-yu Tian, M.D.,zhoudong66@yahoo.de or tianlinyu@sina.com.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 81301659, 81401077.

摘要:

脓毒症幸存者易存在慢性认知功能障碍,而海马神经元缺失与认知功能损害有关,但其具体机制尚不可知。试验以盲肠结扎穿孔方法诱导构建脓毒症小鼠模型,结果发现造模后14,60d时脓毒症小鼠Akt,mTOR和p70S6K磷酸化水平增加,海马CA1区神经元缺失严重,且神经元形态出现异常。提示脓毒症后海马神经元形态与数量的变化与Akt/mTOR信号通路高度激活有关,可能是脓毒症后神经元丢失 “自我拯救”反应的反馈。

orcid:0000-0001-7101-4125(Dong Zhou)

关键词: 神经再生, 脓毒症, 认知障碍, Akt, mTOR, p70S6K, 海马, 神经元, 磷酸化, 神经肥大

Abstract:

Survivors of sepsis may suffer chronic cognitive impairment as a long-term sequela. However, the precise mechanisms of cognitive dysfunction after sepsis are not well understood. We employed the cecal ligation-and-puncture-induced septic mouse model. We observed elevated phosphorylation of Akt, mammalian target of rapamycin (mTOR) and p70S6K on days 14 and 60, progressive neuronal loss in the cornu ammonis 1 region, and abnormal neuronal morphology in the hippocampus in the sepsis mouse model. These findings indicate that changes in neuronal morphology and number in the hippocampus after sepsis were associated with strong activation of the Akt/mTOR signaling pathway, and may reflect a “self-rescuing” feedback response to neuronal loss after sepsis.

Key words: nerve regeneration, sepsis, cognitive impairment, Akt, mTOR, p70S6K, hippocampus, neurons, phosphorylation, neural hypertrophy, neural regeneration