Study On The Reactivity Of Neuronal Somas Of Injured Central And Peripheral Nerves

Adult mammalian neurons in peripheral nervous system (PNS) differ from that in central nervous system (CNS) in their response to injury, the former can successfully regenerate while the latter can not after axotomy. Therefore, there are important theoretical and applied values in understanding the mechanisms related to regeneration and degeneration of central nervous system and finding out the effective therapeutic tool by investigating and analyzing the difference of the injury and repair process of the central and peripheral nerves.The research about CNS regeneration has been emphasized on the role of regeneration microenvironment, nevertheless no dramatic improvements in nervous regeneration and functional recovery has been achieved in clinical treatment. Since the injured axonal somas would occur a series of responses including functional, structural and molecular constitutes changes, and also the materials used for nerve regeneration would be synthesized by the soma, we investigated the differences in morphology, FTIR . and gene expression pattern between central and peripheral neuronal soma areas following CNS and PNS axons injured by means of sciatic nerve crush and hemisection of the spinal cord as the models for reproducible in PNS and un-reproducible in CNS respectively. The research contents and main results were as follows:Following hemisection of the spinal cord, the injured contralateral corticospinal cord neurons showed degenerated changes: the electronic density of cytoplasm was decreased, the number of subcellular constitutes significantly decreased and degenerated, and more TUNEL- positive cells presented; there were increased "neurone phagia" phenomenon in injured corresponding side. These results suggested that following the distal axotomy in CNS the neurons and glials distributed in soma area got affected, which not only was a response to injury, but also related toincapable of regeneration. 'The analysis data of infrared spectroscopy indicated that there were some differences in changes of nucleic acid and protein contents between PNS and CNS: at the 7th day after both PNS and CNS injury, the contents of DNA, RNA, and protein of neuron areas increased; 7 days latter after injury, the changes of DNA, RNA, and protein differ: DNA and RNA contents in PNS neurons remained high and that in CNS recovered. The changes of protein content in PNS and CNS were opposite. The results revealed that the responsibility of neuronal somas in PNS and CNS were different following injury, which might be associated with the difference of regenerative ability between PNS and CNS injury.The gene expression pattern in neuronal somas of the PNS and CNS following axon injury were identified and compared by cDNA microarray profiling techniques. It was found that there were significantly different gene expression pattern in PNS and CNS: the kind of gene expressed in the neuronal soma area in CNS were more than that in PNS under the control; the gene expression patterns of PNS and CNS were obviously different after their being injured. The changed genes can be clarified into three types: up-regulated genes, down-regulated genes and opposite regulated genes, which associated with cell proliferation, transcription regulation, apoptosis, growth and signal transduction. The results indicated that there existed different gene expression patterns to control the different biological process in PNS and CNS, and different molecular mechanism to influence regenerating process in PNS and CNS. This dissimilarity might mediate distinct physiological or pathological processes to result in distinct consequences.The expression change of several selected genes in L4-6 segment of sciatic nerve ligation was compared with that of sciatic nerve crush and that in cerebral cortex of spinal cord hemisection. There was difference of gene expression among the three injury models. The analysis data indicated that the response of same neuron to different stimulation was varied and the response of the different neuron to similar stimulation was different too. It revealed that the factors affecting nerve regeneration possesseddiversity and complexity.From the above results, it indicates that there is substantial differentiation between PNS and CNS in response to injury. It is helpful for us to understand the molecular mechanism leading to the regeneration difference between PNS and CNS and the role of neuron soma in nerve regeneration. Moreover, we could identify the molecules associating with regulating regeneration or cooperating with others, which would supply the clues for screening the pharmacological targets promoting nerve regeneration.