INTRATHECAL APPLICATION OF SHORT INTERFERING RNA KNOCKS DOWN C-JUN EXPRESSION AND AUGMENTS SPINAL MOTONEURON DEATH AFTER ROOT AVULSION IN ADULT RATS

被引：21
作者：
Cheng, X. [1 ]
Fu, R. [1 ]
Gao, M. [2 ]
Liu, S. [1 ]
Li, Y. -Q. [1 ]
Song, F. -H. [1 ]
Bruce, I. C. [5 ]
Zhou, L. -H. [1 ]
Wu, W. [2 ,3 ,4 ]
机构：
[1] Sun Yat Sen Univ, Zhong Shan Sch Med, Dept Anat, Guangzhou 510080, Guangdong, Peoples R China
[2] Univ Hong Kong, Li Ka Shing Fac Med, Dept Anat, Pokfulam, Hong Kong, Peoples R China
[3] Univ Hong Kong, State Key Lab Brain & Cognit Sci, Pokfulam, Hong Kong, Peoples R China
[4] Jinan Univ, GHM Inst CNS Regenerat, Guangzhou, Guangdong, Peoples R China
[5] Zhejiang Univ, Sch Med, Dept Physiol, Hangzhou 310003, Zhejiang, Peoples R China
来源：
NEUROSCIENCE | 2013年 / 241卷
基金：
美国国家科学基金会;
关键词：
c-jun; regeneration; gene silencing; motoneurons; root avulsion; RNA interference; NITRIC-OXIDE SYNTHASE; GENE-EXPRESSION; TRANSCRIPTION FACTORS; NEUROTROPHIC FACTOR; ALZHEIMERS-DISEASE; NERVOUS-SYSTEM; AXONAL INJURY; CELL-DEATH; NEURONS; PROTEINS;
D O I：
10.1016/j.neuroscience.2013.03.006
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
The immediate-early gene, c-jun, is expressed in spinal motoneurons after spinal root avulsion. The expression of c-jun was suggested to be necessary for motoneuron survival and regeneration after avulsion. In the present study, a small interfering RNA (siRNA) was delivered intrathecally to the injured spinal segments immediately after root avulsion in rats to knock down expression of the c-jun gene in injured spinal motoneurons so as to explore the role of c-jun in the motoneurons in vivo. Our results showed that the siRNA not only inhibited the expression of both c-jun mRNA and protein but also augmented the death of injured motoneurons at day 14 post-injury. These findings indicated that induction of c-jun gene expression plays a pivotal role in the survival of injured motoneurons. Meanwhile, these results suggest that siRNAs applied intrathecally can effectively mediate the expression of the c-jun gene in injured motoneurons. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码：268 / 279
页数：12
相关论文
共 46 条
[1]   Delivery systems for the direct application of siRNAs to induce RNA interference (RNAi) in vivo [J].
Aigner, Achim .
JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY, 2006,
[2]  
ANDERSON AJ, 1995, J NEUROCHEM, V65, P1487
[3]   INCREASED IMMUNOREACTIVITY FOR JUN-RELATED AND FOS-RELATED PROTEINS IN ALZHEIMERS-DISEASE - ASSOCIATION WITH PATHOLOGY [J].
ANDERSON, AJ ;
CUMMINGS, BJ ;
COTMAN, CW .
EXPERIMENTAL NEUROLOGY, 1994, 125 (02) :286-295
[4]   THE ROLE OF JUN, FOS AND THE AP-1 COMPLEX IN CELL-PROLIFERATION AND TRANSFORMATION [J].
ANGEL, P ;
KARIN, M .
BIOCHIMICA ET BIOPHYSICA ACTA, 1991, 1072 (2-3) :129-157
[5]   RNAi therapeutics: a potential new class of pharmaceutical drugs [J].
Bumcrot, David ;
Manoharan, Muthiah ;
Koteliansky, Victor ;
Sah, Dinah W. Y. .
NATURE CHEMICAL BIOLOGY, 2006, 2 (12) :711-719
[6]   c-Jun regulation in rat neonatal motoneurons postaxotomy [J].
Casanovas, A ;
Ribera, J ;
Hager, G ;
Kreutzberg, GW ;
Esquerda, JE .
JOURNAL OF NEUROSCIENCE RESEARCH, 2001, 63 (06) :469-479
[7]   EGb761 protects motoneurons against avulsion-induced oxidative stress in rats [J].
Cheng, Xiao ;
Liu, Fo-Lin ;
Zhang, Jun ;
Wang, Lin-Lin ;
Li, Fang-Lan ;
Liu, Shu ;
Zhou, Li-Hua .
JOURNAL OF BRACHIAL PLEXUS AND PERIPHERAL NERVE INJURY, 2010, 5 (01)
[8]  
De Fougerolles A, 2005, METHOD ENZYMOL, V392, P278
[9]   siRNA relieves chronic neuropathic pain [J].
Dorn, G ;
Patel, S ;
Wotherspoon, G ;
Hemmings-Mieszczak, M ;
Barclay, J ;
Natt, FJC ;
Martin, P ;
Bevan, S ;
Fox, A ;
Ganju, P ;
Wishart, W ;
Hall, J .
NUCLEIC ACIDS RESEARCH, 2004, 32 (05) :e49
[10]   IS C-JUN INVOLVED IN NERVE-CELL DEATH FOLLOWING STATUS EPILEPTICUS AND HYPOXIC-ISCHEMIC BRAIN INJURY [J].
DRAGUNOW, M ;
YOUNG, D ;
HUGHES, P ;
MACGIBBON, G ;
LAWLOR, P ;
SINGLETON, K ;
SIRIMANNE, E ;
BEILHARZ, E ;
GLUCKMAN, P .
MOLECULAR BRAIN RESEARCH, 1993, 18 (04) :347-352
12345