Abstract:

Abstract:Objective
 To investigate the effects of antidepressant venlafaxine on the apoptotic cell percentage,death rate and cell cycle of the hippocampus neurons injured by glutamate(Glu) and demonstrate the neuroprotection mechanism of   venlafaxine.Methods The primary cultured hippocampal neurons were used  to set up Glu injured model.Three groups were included in the experiment: control group,Glu model group and venlafaxine administration group.The changes in apoptotic cell percentage,death rate and cell cycle of neurons were detected respectively by FCM before and after administration with venlafaxine.Results The apoptotic cell percentage in Glu model group was increasd compared with control group (P<0.01),but venlafaxine could reverse it.Compared with Glu model group,in venlafaxine administration group the    apoptosis was suppressed at low concentrations,the apoptotic cell percentage was decreased at 10  μmol·L^-1 venlafaxine （P<0.05),nevertheless,the   apoptosis was promoted at high concentrations,the apoptotic cell percentage was increased dramatically when treated with  100  μmol·L^-1 venlafaxine  (P<0.01).The  death rate of neurons in Glu model group was increased compared  with control group(P<0.05 ),the death rate of neurons  was reduced in venlafaxine administration group  compared with  Glu model group (P<0.05 or P<0.01).Compared with control group,the apoptotic cell percentage of G0/G1 phase in Glu model group was increased (P<0.001),the apoptotic cell percentage of S phase was decreased (P<0.01),the cell percentages of G_²+M phase   didn’t change significantly.The  apoptotic cell percentages in venlafaxine administration groups showed an decreasing trend at G₀/G₁ phase,which decresed to 64.5% and 50.8% of  that in Glu model groups when treated with  100 and 200  μmol·L^-1  venlafaxine (P<0.05).The apoptotic cell percentages of  S phase in venlafaxine administration groups were increased,which were 3.6,4.7 and 4.2 times of that in Glu model group when treated with 100,200 and 500  μmol·L^-1 venlafaxine respectively (P<0.01).Conclusion Venlafaxine can prevent the hippocampal neurons from the damage induced with Glu,elevate the neuron survival rate,reduce the LDH release,keep the cell membrane intact,and decrease the apoptotic cell percentage and death rate of neurons,which has the neuroprotection.

Key words:  venlafaxine;neuroprotection;glutamate;neuron