The Effects Of Schwann Cells On Motor Nerve Damage And Repair Inuced By Acrylamide

Acrylamide (ACR) is a synthetic monomer with a wide scope of industrial applications. In addition to occupational exposure of ACR, the general population can also be exposed to ACR via food and drinking water contaminated by ACR. Diseases of peripheral nervous system can be caused under long-term exposure of ACR with low concentrations, of which the major symptom was sensory-motory peripheral neuropathy.Schwann cells (Scs) is the unique glial cell of peripheral nervous system around neurons. It's full of constructive function, which plays a key role in survival, repair and regeneration of peripheral nervous system. Under normal condition, Scs could provide nutritional support for the neurons of peripheral system. As soon as peripheral nerve is damaged, Scs could proliferate, secrete neurotrophic factors and produce extracellular matrix and cell adhesion molecules, which can construct a suitable microenvironment for regenerative process.In the past few years, the studies on ACR neurotoxicity have been paied less attenion to the Scs function in the procedure of action, especially the changes of the neurotrophic factors excreted by Scs and the possible interaction between these proteins during exposure of ACR. This research is to study the effects of Scs on motor nerve damage and repair induced by ACR using cell model, and to detect the changes in protein translation and gene expression in Scs in the co-culture with motoneuron, in order to proclaim the function of Scs in the damage and repair of motoneuron exposed to ACR and pathway of toxicity.1. Cell culture modelTo contruct a model of Co-culture of primary Scs and motoneuron cell line VSC4.1 with culture plate filter inserts. 2. The protective effects of Scs on VSC4.1 in the process of damage and repair in ACR exposure.1) Results of MTT tests showed that IC50 of VSC4.1 treated with ACR for 24h was 329μg/ml, and for the co-cultured VSC4.1 was 558μg/ml, thus Scs has increased the IC50 of VSC4.1. Compared with the non co-cultured VSC4.1, the relative survival rates of co-cultured VSC4.1 were increased in the test groups of 100,200,300,400,500 and 600μg/ml (P＜0.05);2) Compared with the non co-cultured VSC4.1, the activity of AchE of co-cultured VSC4.1 increased (P＜0.05) in the process of both injury and repair, and so did the expression of GAP-43.3. Different translation of target proteins in Scs damaged by ACR Compared with the control group, the level of NGF was increased, and that of P75 was declined, but the change of of TrkA has not detected yet.4. Different expression of target gene in Scs impaired by ACR1) Changes on NGF mRNA expression during the test phase in ACR-impaired-Scs:After exposure to ACR for 24h (final concentration was 40μg/ml), the Scs repairing for 24h and 48h, Scs NGF mRNA level increased first, then decreased, and increase at last;2) Changes on TrkA mRNA expression during the test phase in ACR-impaired-Scs:After exposure to ACR for 24h (final concentration was 40μg/ml), the Scs repairing for 24h and 48h, Scs TrkA mRNA level increased first, then decreased, and increase at last;3) Changes on P75 mRNA expression during the test phase in ACR-impaired-Scs:After exposure to ACR for 24h (final concentration was 40μg/ml),the Scs repairing for 24h and 48h, Scs P75 mRNA level increased first, then decreased, and increase at last;4) Changes on BDNF mRNA expression during the test phase in ACR-impaired-Scs:Scs BDNF mRNA level was decreased during repair;5) Changes on CNTF mRNA expression during the test phase in ACR-impaired-Scs:After exposure to ACR for 24h (final concentration was 40μg/ml), the Scs repairing for 24h and 48h, Scs CNTF mRNA level decreased and then began to increase at repairing;6) Changes on GDNF mRNA expression during the test phase in ACR-impaired-Scs:Scs GDNF mRNA level was decreased during the test.7) Changes on NCAM mRNA expression during the test phase in ACR-impaired-Scs:After exposure to ACR for 24h (final concentration was 40μg/ml), the Scs repairing for 24h and 48h, Scs NCAM mRNA level increased first, then decreased, and increase at last.In conclusion, this study has proved that Scs played a protective effect on the injury of VSC4.1 induced by ACR during the process of injury and repair.According to the changes of genes expression and proteins translation involved in procedure of Scs protecting, it was might be concluded:First in the protein translation, the up-regulation of NGF and down-regulation of P75 may be the possible pathway for Scs resisting the ACR neurotoxicityand promoting the repair of ACR-impaired-motoneuron; Second in the gene expression, the up-regulation of TrkA, CNTF and NCAM could be the possible target of Scs protecting the motor never, the down-regulation of BDNF and GDNF may indicate that ACR would suppress expression of these genes specificly. The findings above might be useful for the prevention and treatment of ACR neurotoxicity.