Crocker S J, Lamba W R, Smith P D, Callaghan S M, Slack R S, Anisman H, Park D S
Neuroscience Research Institute, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Proc Natl Acad Sci U S A. 2001 Nov 6;98(23):13385-90. doi: 10.1073/pnas.231177098. Epub 2001 Oct 30.
Expression of the transcription factor c-Jun is induced in neurons of the central nervous system (CNS) in response to injury. Mechanical transection of the nigrostriatal pathway at the medial forebrain bundle (MFB) results in the delayed retrograde degeneration of the dopamine neurons in the substantia nigra pars compacta (SNc) and induces protracted expression and phosphorylation of c-Jun. However, the role of c-Jun after axotomy of CNS neurons is unclear. Here, we show that adenovirus-mediated expression of a dominant negative form of c-Jun (Ad.c-JunDN) inhibited axotomy-induced dopamine neuron death and attenuated phosphorylation of c-Jun in nigral neurons. Ad.c-JunDN also delayed the degeneration of dopaminergic nigral axons in the striatum after MFB axotomy. Taken together, these findings suggest that activation of c-Jun mediates the loss of dopamine neurons after axotomy injury.
转录因子c-Jun的表达在中枢神经系统(CNS)的神经元中因损伤而被诱导。在内侧前脑束(MFB)处对黑质纹状体通路进行机械横断会导致黑质致密部(SNc)中多巴胺能神经元的延迟逆行性变性,并诱导c-Jun的持续表达和磷酸化。然而,CNS神经元轴突切断后c-Jun的作用尚不清楚。在此,我们表明腺病毒介导的c-Jun显性负性形式(Ad.c-JunDN)的表达抑制了轴突切断诱导的多巴胺能神经元死亡,并减弱了黑质神经元中c-Jun的磷酸化。Ad.c-JunDN还延迟了MFB轴突切断后纹状体中多巴胺能黑质轴突的变性。综上所述,这些发现表明c-Jun的激活介导了轴突切断损伤后多巴胺能神经元的丧失。