title: C-jun phosphorylation contributes to down regulation of neuronal nitric oxide synthase protein and motoneurons death in injured spinal cords following root-avulsion of the brachial plexus.
abstract: Previous studies have shown that c-jun and neuronal nitric oxide synthase (nNOS) are both induced in injured motoneurons, but their roles in motoneuron death remain unclear. We hypothesized that nNOS might be the downstream effector of c-jun N-terminal kinase (JNK)/c-jun in avulsion-induced motoneuron death. Here, we found that brachial root-avulsion induced a temporary increase in JNK activity and three- and four-fold increases in phospho-c-jun and c-jun, respectively; however, brachial root-avulsion caused a decrease in nNOS protein expression from 4 h to 14 days post-injury. At 14 days post-injury, almost all nNOS-positive motoneurons were co-localized with phospho-c-jun-positive motoneurons in ipsilateral ventral horns. The JNK inhibitor SP600125, applied immediately post-injury, resulted in an upregulation of nNOS protein both in injured spinal cords and motoneurons and caused a slight alleviation of motoneuron death by inhibiting c-jun phosphorylation at 14 days post-injury. Our results demonstrated that the JNK/c-jun signal transduction pathway is involved in root-avulsion. The inhibition of c-jun phosphorylation prevents nNOS levels from dropping below baseline levels in the spinal cord and partially alleviates motoneuron death following root-avulsion. Therefore, inhibiting c-jun phosphorylation or up-regulating the nNOS protein in injured spinal cords at the early stage might be used in the future as the molecular-target strategies to prevent the motoneurons degeneration in root-avulsion.
authors: Zhong Shan School of Medicine, Sun Yat-Sen University, No. 74 Zhongshan Road 2, Guangzhou 510080, PR China.
authors: L-L
authors: LL
authors: Wang
authors: X-C
authors: XC
authors: Zhao
authors: L-F
authors: LF
authors: Yan
authors: Y-Q
authors: YQ
authors: Wang
authors: X
authors: X
authors: Cheng
authors: R
authors: R
authors: Fu
authors: L-H
authors: LH
authors: Zhou