中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (1): 150-157.doi: 10.4103/1673-5374.286976

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

脑源性神经营养因子可保护丙烯酰胺诱导的神经元和突触损伤

  

  • 出版日期:2021-01-15 发布日期:2020-11-26
  • 基金资助:

    国家自然科学基金项目(81773474,81273110);国家重点研究发展项目(2017YFF0211201)

Brain-derived neurotrophic factor protects against acrylamide-induced neuronal and synaptic injury via the TrkB-MAPK-Erk1/2 pathway

Xiao Chen1, #, Jing-Wei Xiao1, #, Peng Cao1, Yi Zhang1, Wen-Jian Cai1, Jia-Yang Song1, Wei-Min Gao2, *, Bin Li1, *   

  1. 1 Department of Toxicology, Key Lab of Chemical Safety and Health, National Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China;   2 Department of Occupational and Environmental Health Sciences, School of Public Health, West Virginia University, Morgantown, WV, USA
  • Online:2021-01-15 Published:2020-11-26
  • Contact: Bin Li, MS, binli65111@hotmail.com; Wei-Min Gao, PhD, weimin.gao@hsc.wvu.edu. #Both authors contributed equally to this work.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, Nos. 81773474 and 81273110 (to BL); the National Key Research and Development Project of China, No. 2017YFF0211201 (to BL).

摘要:

丙烯酰胺具有神经毒性,而脑源性神经营养因子可在一定范围内减轻丙烯酰胺引起的突触损伤,但作用机制尚不明确。(1)实验首先以0-100μg/mL丙烯酰胺干预24-72h干预经db-cAMP诱导分化成熟的人神经母细胞瘤细胞系模型(NB-1细胞),发现丙烯酰胺可以剂量和时间依赖性方式降低细胞活力并破坏突触;(2)在与许旺细胞共培养的NB-1细胞中,以0-100μg/mL丙烯酰胺干预48h,可使突触素I和脑源性神经营养因子表达上调,即许旺细胞可激活神经元的自我保护。在共培养条件下,TrkB-MAPK-Erk1/2通路下游激活可增强该保护作用;(3) 外源性脑源性神经营养因子可引起TrkB,Erk1/2和突触蛋白I表达升高,而外源脑源性神经营养因子或TrkB抑制剂K252a可抑制上述变化;(4)综上,许旺细胞可能通过脑源性神经营养因子-TrkB-MAPK-Erk1/2信号通路发挥起作用,说明脑源性神经营养因子在这一过程中发挥了重要作用,因而添加外源性脑源性神经营养因子可能成为丙烯酰胺诱导神经损伤的有效治疗途径。实验于2017年5月29日获得中国疾病预防控制中心职业卫生与中毒控制所实验动物福利和道德委员会批准(EACD-2017-008)。

https://orcid.org/0000-0001-8562-8697 (Bin Li); 

0000-0001-6407-3258 (Wei-Min Gao)

关键词: 周围神经, 再生, 蛋白, 因子, 通路, 损伤, 修复, 保护

Abstract: Acrylamide has been shown to be neurotoxic. Brain-derived neurotrophic factor (BDNF) can alleviate acrylamide-induced synaptic injury; however, the underlying mechanism remains unclear. In this study, dibutyryl-cyclic adenosine monophosphate-induced mature human neuroblastoma (NB-1) cells were exposed with 0–100 μg/mL acrylamide for 24–72 hours. Acrylamide decreased cell viability and destroyed synapses. Exposure of co-cultured NB-1 cells and Schwann cells to 0–100 μg/mL acrylamide for 48 hours resulted in upregulated expression of synapsin I and BDNF, suggesting that Schwann cells can activate self-protection of neurons. Under co-culture conditions, activation of the downstream TrkB-MAPK-Erk1/2 pathway strengthened the protective effect. Exogenous BDNF can increase expression of TrkB, Erk1/2, and synapsin I, while exogenous BDNF or the TrkB inhibitor K252a could inhibit these changes. Taken together, Schwann cells may act through the BDNF-TrkB-MAPK-Erk1/2 signaling pathway, indicating that BDNF plays an important role in this process. Therefore, exogenous BDNF may be an effective treatment strategy for acrylamide-induced nerve injury. This study was approved by the Laboratory Animal Welfare and Ethics Committee of the National Institute of Occupational Health and Poison Control, a division of the Chinese Center for Disease Control and Prevention (approval No. EAWE-2017-008) on May 29, 2017.

Key words: factor, injury, pathway, peripheral nerve, protection, protein, regeneration, repair