journal1 ›› 2013, Vol. 21 ›› Issue (10): 1049-1051.

Previous Articles     Next Articles

Neuronal protective effect of brain-derived neurotrophic factor mediate by autophagy through PI3K/Akt/mTOR pathway

CHEN Ai1,2,3,4,XIONG Li-jing1,2,3,MA Jiao1,2,3,TONG Yu2,3,MAO Meng1,2,3   

  1. 1 Department of Pediatrics,West China Second University Hospital,Sichuan University,Chengdu,Sichuan 610041,China; 2 Laboratory of Early Developmental and Injuries,West China Institute of Woman and Children's Health,West China Second University Hospital,Sichuan University,Chengdu,Sichuan 610041,China; 3.Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education,Chengdu,Sichuan 610041,China; 4.Department of Pediatrics,the Affiliated Hospital of Luzhou Medical College,Luzhou,Sichuan 646000,China
  • Received:2013-03-18 Online:2013-10-06 Published:2013-10-06
  • Contact: MAO Meng,E-mail:dffmmao@126.com

脑源性神经营养因子通过PI3K/Akt/mTOR信号途径对胚鼠缺氧神经元的保护作用

陈艾1,2,3,4,熊励晶1,2,3,马骄1,2,3,童煜2,3,毛萌1,2,3   

  1. 1 四川大学华西第二医院儿科,四川 成都 610041; 2 四川大学华西第二医院西部妇幼医学研究院妇儿疾病与出生缺陷教育部重点实验室,早期发育与损伤重点实验室,四川 成都 610041; 3 发育与妇儿疾病四川省重点实验室,四川 成都 610041; 4 泸州医学院附属医院儿科,四川 泸州 646000
  • 通讯作者: 毛萌,E-mail:dffmmao@126.com
  • 作者简介:陈艾,女,主治医师,在读博士,研究方向为小儿神经康复。
  • 基金资助:
    国家自然科学基金(30973215);四川省科技支撑计划(2012SZ0010);教育部创新团队和新世纪人才计划(IRT 0935)

Abstract: Objective Based on growing evidence linking autophagy to ischemic preconditioning,it was hypothesized that autophagy was necessary for neuroprotection conferred by hypoxic preconditioning and further aimed to test whether brain-derived neurotrophic factor(BDNF) protects against hypoxic neuronal damage by autophagy activation and the possible signaling pathway. Methods Primary cultured cortical neurons of pregnant rats were treated with oxygen deprivation (OD) for 0.5~6 h to mimic hypoxic injury in vivo.Neuronal autophagy was measured with expression of microtubule associated protein light chain 3(LC3),and the LC3II,p-Akt,p-mTOR,and p-p70S6K protein were detected by western-blot after treated with autophagy promotor rapamycin or autophagy inhibitor 3-methyladenine(3-MA). Results 1)Compared with the control group,cells treated with 50 μg/L BDNF had the highest cell viability.2)BDNF decreased the expression of P-Akt,p-mTOR,and p-p70S6K,and increased the expression of LC3II.Similar to the roles of rapamycin to the signals,BDNF-induced up-regulation of LC3II was inhibited by 3-MA. Conclusion BDNF protects cortical neurons against oxygen deprivation damage by autophagy via PI3K/Akt/mTOR/p70S6K signaling pathway.

Key words: brain-derived neurotrophic factor, autophagy, cortical neurons, mammalian target of rapamycin, light chain 3

摘要: 目的 探讨脑源性神经生长因子(brain-derived neurotrophic factor,BDNF)对缺氧(oxygen deprivation,OD)神经元的保护作用是否与激活自噬有关,其信号通路是否通过PI3K/Akt/mTOR途径。方法 1)建立胚鼠神经元OD损伤模型;CCK-8法观察不同浓度BDNF对OD神经元细胞活性的影响;2)检测OD神经元1,3,5 h自噬微管相关蛋白轻链3(LC3)的表达,情况观察BDNF对OD神经元的保护作用是否与自噬有关;3)检测p-Akt,p-mTOR,p-p70S6K以及LC3II的表达,对比BDNF与自噬激活剂雷帕霉素(mammalian target of rapamycin,Rapamycin)对Akt/mTOR/p70S6K的影响,以及自噬被3-MA抑制后,BDNF对Akt/mTOR/p70S6K的影响。结果 1)50 μg/L BDNF可对OD神经元起保护作用(P<0.05),100 μg/L BDNF效应次之;2)BDNF和/或Rapamycin在下调p-Akt/p-mTOR/p-p70S6K表达的同时可上调LC3II的表达;当3-MA抑制自噬后,BDNF对LC3II的上调作用被抑制。结论 BDNF通过PI3K/Akt/mTOR/p70S6K信号途径激活自噬,发挥对OD神经元的保护作用。

关键词: 脑源性神经生长因子, 自噬, 神经元, 哺乳动物雷帕霉素靶蛋白, 自噬微管相关蛋白轻链3

CLC Number: