The Signal Transduction And Associated Factors During Facial Nerve Injury And Regeneration

The facial nerve is the most frequently affected nerve in head-neck trauma and surgery, but the functional recovery remains poor. So studies of signal transduction and associated factors during facial nerve injury and regeneration are important in understanding its mechanism. Acetylcholine (Ach) is a crucial neurotransmitter for the motoneurons that innervate skeletal muscles. It is synthesized by choline acetyltransferase (ChAT) and transported into synaptic vesicles by vesicular acetylcholine (VAChT). ChAT is presently the most specific indicator for monoitoring the functional state of cholinergic neurons in the central and peripheral nervous systems. It was found the entire VAChT gene is located within the first intron of the ChAT gene in the same transcriptional orientation. The expression of ChAT and VAChT appear to be coordinately regulated by multiple factors in the cholinergic neurons. Neurotrophic factors(NTs) play an important role in the development, maintenance and plasticity of the nervous system. They bind, dimerize, and thereby activate protein tyrosine kinase receptor of the trk family. The interactions appear to mediate the major biological function of NTs. IL-6 type cytokines belong to neuropoietic cytokine family, have a similar role as NTs in nervous system. It was found that these cytokines signal via the activation of Janus kinascs (Jaks) and transcription factors of the STAT family. The signaltransfer of NTs and cytokines involved several steps of protein phosphoration. The reversible phosphoration and dephosphoration play important roles in singnal transduction. While facial nerve reinnervation, the synkinesis always inevitable occur, but its mechanism is still unknown.In present studies, we employed the facial nerve transection and immediate end-to-end anastomosis as models for facial nerve degeneration and regeneration in the rat and attampted to examine the time course of the changes of ChAT, VAChT, trkB, trkC, STATS in motoneurons of the facial nucleus following peripheral nerve transection and end-to-end anastomosis by using in situ hybridization, RT-PCR and immunohistochemical staining, to examine the distribution of motoneurons innervated buccall and marginal mandibular branches, and its reorganization after facial nerve reinnervation.Part 1 Changes of ChAT and VAChT in facial motoneurons after axotomy and end-to-end anastomsis in the ratThe facial nerve regeneration occurs between 2 and 5 weeks in group of anastomsis by observing the restoration of rhythmical whisking. By 35 days symmetrical whisking activity was attained bilaterally. Transection of the facial nerve resulted in a striking reduction in both number of ChAT/VAChT immunoreactive neurons and optical density of ChAT/VAChT immunostaining in the facial nucleus ipsilateral to the operation. A maximal decrease in these values was observed 7 days after operation. The patterns of reduction in both number of ChAT/VAChT immunoreactive neurons and optical density of ChAT/VAChT immunostaining following an immediate end-to-end anastomosis within 7 days post-operation were similar to that of transection group. These values began to increase at the time point of 14 days afteranastomosis. Thirty-five days after anastomosis, ChAT/VAChT immunostaining intensity return to normal level. Our results indicate that an immediate end-to-end anastomosis of the transected facial nerve is unable to attenuate the maximal decrease of ChAT/VAChT immunoreactivity within 7 days post-operation. The successful return of axotomy-induced decrease of ChAT/VAChT immunoreactivity in facial motoneurons occurs following facial nerve to sprout and reinnervate the denervated facial muscles. The expression of ChAT and VAChT in the facial motoneurons appear to be coordinately regulated after facial nerve transection.Part 2 Changes of trkB and trkC in facial motoneurons after axotomy and end-to-end anastomsis in the ratTransection of the facial nerve resulted in a upregulation of trkB, but a downregulation of trkC in both mRNA and pro...