The Neuron Injury Effect Of Glucocorticoid And The Possible Mechanism

Objective:The thesis study the possible mechanisim of the neuron injury effect caused by glucocorticoid(GC), mainly focused on the cellular prion protein's fuction in the injury process in order to explore the mechanism of depression and the new way to cure depression disease.Method:We took out the hippocampus of the newborn rats within24hours and cultured its primary cells. Using polymerase chain reaction (PCR)^Western Blot(WB),Immunofluorescence and mono-nuclear cell direct cytotoxicity assay (MTT) to detect the hippocampal neuron's injury which caused by GC and the change of relevant proteins'expression. Then we set up animal model of chronic stress depression and detect the expression of PrPc in different areas of the brain, including hippocampus,cortex,midbrain and striatum. What's more, we observed the injury caused by GC in SH-SY5Y by MTT method, detected the change of PrPc's expression after different times'treatment and observed whether SH-SY5Y cells would be more easily get injured by NMDA after GC's treatment. We also using virus transfection to knock-down PrPc gene, then detected its transfecton efficiency by WB and observed whether the excited extend changed.Result:The expression of NR2A and NR2B in the hippocampal primary neurons increased after GC's treatment while GR decreased obviously and MR had a slightly decreased. We also found that PrPc's expression decreased. The expression of PrPc decreased in the hippocampus,cortex and striatum of the chronic stress depression model. After different time's treatment by GC, PrPc's expression increased at first and then decreased in the wildtype SH-SY5Y cells. After long time GC's treatment, SH-SY5Y cells will be much easier to be injured by NMDA. SiPrP is much easier to be injured by NMDA than SiLuc.Conclusion:PrPc's expression decreased in the neuron cells after long time GC treatment. The mechanism maybe relevant to the activated of NMDAR and caused the injury of neuron cells.