c-Jun mediates axotomy-induced dopamine neuron death in vivo

Expression of the transcription factor c-Jun is induced in neurons of the c entral nervous system (CNS) in response to injury. Mechanical transection o f the nigrostriatal pathway at the medial forebrain bundle (MFB) results in the delayed retrograde degeneration of the dopamine neurons In the substan tia nigra pars compacta (SNc) and induces protracted expression and phospho rylation 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 neu ron death and attenuated phosphorylation of c-Jun in nigral neurons. Ad.c-J unDN also delayed the degeneration of dopaminergic nigral axons in the stri atum after MFB axotomy. Taken together, these findings suggest that activat ion of c-Jun mediates the loss of dopamine neurons after axotomy injury.