Protective Effects And Mechanisms Of Se-methyl-seleno-L-cysteine On The Apoptosis Of Neural Stem Cells Caused By Aβ_1-42

β-amyloid (Aβ) protein is the main component of senile plaques. It is widely thought that the aggregation of Aβis the major reason of the incidence of Alzheimer's disease. AP aggregation has severe neural toxicity. Recent studies showed that, as one of essential traces to human body, the element of selenium has a protective effect on neurotoxicity. In view of this, this study explored protective effects and the underlying mechanisms of Se-methyl-seleno-L-cysteine on the apoptosis of NSCs caused by Aβ1-42 through a series of in vitro assays, which is benifical for furhter understanding the role of Aβto neurogenesis and will provide a reliable theoretical basis and experimental support for the treatment of AD and other neurodegenerative diseases by NSCs.The brain of 1-day newborn ICR mouse is taken out, from which NSCs is obtained by mechanical separation. The cells were subcultured and identified by immunohistochemical staining and RT-PCR methods. The NSCs were treated by 1μg/mL,5μg/mL,10μg/mL,50μg/mL of Se-methyl-seleno-L-cysteine respectively for 24 h, and then the aggregated Aβ1-42 oligomers(10μmol/L) were added to the corresponding experimental group for 12 h,24 h and 48 h respectively. The cell proliferation and apoptosis were detected using MTT assay and flow cytometry. Then, the protection mechanism of Se-methyl-seleno-L-cysteine against Aβ1-42 oligomer injury to neural stem cell was investigated by detecting the expression of the c-Jun and JNK gene with RT-PCR.The results showed that 1μg/mL,5μg/mL and 10μg/mL Se-methyl-seleno-L-cysteine had no significant effect on the proliferation of NSCs at 12 h,24 h and 48 h, respectively; while,50μg/mL Se-methyl-seleno-L-cysteine inhibited the proliferation of neural stem cell at 12 h,24 h and 48 h; which showed that large-dose Se-methyl-seleno-L-cysteine could injury NSCs. After treated by 10μmol/L AP1-42 and 1μg/mL or 5μg/mL or 10μg/mLor 50μg/mL Se-methyl-seleno-L-cysteine respectively, the result showed that 1μg/mL,5μg/mL and 50μg/mL Se-methyl-seleno-L-cysteine had not significant protective effect on the NSCs injury induced by 10μmol/L Aβ1-42 and that 10μg/mL Se-methyl-seleno-L-cysteine had significant protection effect (p<0.01) at 12 h; and that 1μg/mL,5μg/mL and 10μg/mL Se-methyl-seleno-L-cysteine had highly significant protection effect (p<0.01) on the NSCs injury induced by 10μmol/L Aβ1-42 and that 50μg/mL Se-methyl-seleno-L-cysteine had no significant protection effect (p <0.01) at 24 h; and that 1μg/mL,5μg/mL and 10μg/mL Se-methyl-seleno-L-cysteine had significant protection effect (p<0.05) on the NSCs injury induced by 10μmol/L Aβ1-42 at 48 h, particularly protective effect of 5μg/mL and 10μg/mL Se-methyl-seleno-L-cysteine were extremely significant (p<0.01) and 50μg/mL Se-methyl-seleno-L-cysteine showed no significant effect at 48 h.. Then, the protectiion effect of different time was compared in three concentration groups. The results indicated that 10μg/mL Se-methyl-seleno-L-cysteine had significant protectiion effect on the apoptosis caused by 10μmol/L Aβ1-42 in 48 h,24 h and 12 h (p<0.01); while, the other concentrations of Se-methyl-seleno-L-cysteine did not show a time-dependent differences. About protection mechanism, RT-PCR results showed that, compared with 10μmol/L Aβ1-42 group, the expression of c-Jun and JNK gradually weaken in 10 u mol/L Aβ1-42+1μg/mL Se,10μmol/LAβ1-42+5μg/mL Se,10μmol/L Aβ1-42+10μg/mL Se groups and increased in 10μmol/L Aβ1-42+50μg/mL Se group, which suggested that appropriate dose of Se-methyl-seleno-L-cysteine inhibits the expression of c-Jun and JNK and have a protective effect on the injury of NSCs caused by Aβ1-42.