Study On Neuroprotective Effect Of Antidepressant And Its Mechanisms

The psychiacists have increasingly paid more attentions to the neuroprotective effect of antidepressant nowadays. It is reported that the chronic antidepressant administration enhances the neurogenesis and prompts the neuron sprouting in hippocampus by its neuroprotective effect, which can block or reverse the atrophy and death of hippocampal neurons in depression and stress. In many studies in human and animal, the conclusion has been verified to date. In this dissertation, the influence of four kinds of antidepressant drugs on rat primary cultured hippocampal neurons injured with glutamate to mimic the pathological changes induced by elevated glucocorticoid (GC) levels in depression or stress was studied. The present study is to observe the effects of four kinds of antidepressant drugs on neuron survival, death and apoptosis, and further explore the neuroprotective effect of antidepressants and its mechanism. The study on the neuroprotective effect of antidepressants The influence of antidepressants on neuron survival The neuron proliferation was detected with MTT. The results showed that the survival rate of neurons injured with the excitatory neurotoxicity of glutamate decreased to 48% of the control (p<0.05). However, the survival rates of neurons injured with glutamate increased in varying degree after the administration with four kinds of antidepressants as compared with those in the glutamate group. The effect of olanzapine was the most evident, followed by quetiapine and venlafaxine. The results demonstrate that these antidepressants can prevent the neurons in himppocampus from the damage induced with glutamate and elevate the neurons survival, which indicate that some antidepressants may have direct protective effect contributing to the proliferation and survival of neurons.1.2 The influence of antidepressants on the permeability of neuronal cell membrane The effects of antidepressants on the lactate dehydratase (LDH) release of neurons in hippocampus injured with glutamate were detected. The results showed that the LDH release of neurons injured with glutamate increased significantly, which was 7.4-fold of the control group. However, after administration with four kinds of antidepressants LDH release from neurons injured with glutamate decreased in varying degree as compared with that in the glutamate group. The effect of antidepressants on LDH release was decreased significantly in the lower concentrations of every antidepressant and was not in the higher concentrations. Meantime, olanzapine was more efficient than the other antidepressants. The results imply that the four kinds of antidepressants all can block the injury of neurons induced with glutamate by keeping the intactness of cell membrane, reducing LDH release and increasing the percentage of survival neurons to exhibit the neuroprotective effect of them on neurons.The influence of antidepressants on the neuron deathThe percentages of death neurons in hippocampus were detected with FCM in the experiment. The results showed that the percentages of neurons injured with glutamate increased approximately three-fold of the control. Nevertheless, the administration of four kinds of antidepressants reduced the percentages of neurons injured with glutamate in varying degree as compared with that in the glutamate group. The results demonstrate that four kinds of antidepressants can inhibit the death of neurons induced with glutamate by their neuroprotective effect.The study on the mechanism of the neuroprotective effect of antidepressants2.1 The influence of antidepressants on the cell cycle of neurons The changes in cell cycle and cell proliferation were detected with FCM in the present experiment. We found that the percentages of G0/G1 phase of neurons in happocampus injured with glutamate increased and those of S phase decreased. The results show that glutamate can inhibit the DNA synthesis and neuronal proliferation. In addition, though the change regulations of cell cycle in neurons were different after...