Protective effects of paroxetine on the lipopolysaccharide injured hippocampal-derived neural stem cell

Objective To investigate the effects of paroxetine on the cell viability and expression of the phosphorylated ERK1/2 in lipopolysaccharide LPS injured hippocampal-derived neural stem cells (NSCs). Methods The NSCs were derived from hippocampus of fetal rats,after the primary neurospheres passaged,the cells were divided into sham,LPS and LPS+ paroxetine groups (include 1,5,10 and 20μmol/L concentration),each group was treated with LPS (200μg/L) and different concentrations of paroxetine for 72 h,then the cell viability and the protein level of pERK1/2 were measured by the kit of WST-8 and Western blot,respectively.Furthermore,in order to investigate the role of ERK pathway that involved in the effects of paroxetine,the NSCs were divided into sham,LPS,LPS+ paroxetine groups (include 1,5,and 10μmol/L concentration),U0126,U0126+LPS and U0126+LPS+paroxetine groups (include 1,5,and 10μmol/L concentration),72 h later,the apoptosis rate was measured by Annexin-Ⅴ-FLUOSstaining kit. Results The cell viability in 5μmol/ L paroxetine treated group (0.338±0.016) was higher than LPS group (0.306±0.016) (F=23.019,P<0.01),but there were no significant differences between other paroxetine treated groups and LPS group.When detected by Western blot,the expression of pERK1/2 in paroxetine 5μmol/L treated groups (1.092±0.113) or sham group (0.982±0.131) was significant higher than LPS group (0.749±0.144),respectively (F=6.887,P<0.05).Furthermore,coincide with cell viability,the apoptosis of 5μmol/L treated groups[ (14.42±1.22) %] or sham group[ (13.40±2.87) %] was significant lower than LPS group[ (17.85±1.26) %] by using flow cytometry (F=26.520,P<0.05).U0126 promoted the apoptosis of LPS treated groups,and there was no significant difference between paroxetine+LPS treated groups and LPS group. Conclusions The cellular damage of NSCs injured by LPS could be restrained by paroxetine,which is possibly carried out by affecting ERK1/2 pathway. Key words: Paroxetine; Neural stem cells; Lipopolysaccharides; Phosphorylated ERK1/2