Abstract:

To investigate the effects of antidepressant quetiapine on the apoptosis,necrosis and cell cycle of the hippocampus neurons injured by glutamate (Glu),and to demonstrate the mechanism of quetiapine on nervous system.Methods Primary cultured hippocampal neurons were injured with Glu.Normal control group,Glu injury group and quetiapine (0.1,1.0,10.0,50.0,100.0,200.0， and 500.0  μmol•L^-1 ) group were set up. The changes in apoptosis,necrosis and cell cycle of neurons were detected by FCM before and after administration with quetiapine.Results Compared with normal control group,the percentage of apoptotic neurons in Glu injury group was increasd (P<0.01);compared with Glu injury group，the apoptotic rates in 50.0-200.0  μmol•L^-1 quetiapine groups were decreased (P<0.05，P<0.01).The necrotic  rate in Glu injury group was increased to 2.9 times compared with normal control group (P<0.05 );compared with Glu injury group，the necrotic  rate of neurons in 0.1   μmol•L^-1 quetiapine group was decreased (P<0.05).Compored with normal control group,the percentage of neurons in G0/G1 phase in Glu injury group was increased (P<0.001),the percentage of of neurons in S phase was decreased (P<0.01),and the  percentage of neurons in G2+M phase didn’t change significantly. Compared with Glu injury group，the percentage of neurons in G0/G1 phase in 200.0   μmol•L-1 quetiapine group was decresed,which was  decreased to 68.9% of that in Glu injury group,and the percentage of neurons in S phase was increased to 3.4 times of that in Glu injury group (P<0.05).Conclusion Quetiapine can prevent the hippocampal neurons from the damage induced with Glu,decrease the apoptosis and necrosis,and change the cell cycle.

Key words: quetiapine, cell cycle, apoptosis, glutamate, neuron, neuroprotection