The Mechanism Of Stress On Transmission Of Synaptic And The Effect Of Resveratrol On Stress

Stress refers to the body non-specific response to stimulation of the external environment or any of the harmful factors in the body.The body emerges headache,anxiety,distraction,insomnia,immunity decrease,memory impairment and cognitive dysfunction after stress.Therefore,we should actively study the causes and pathogenesis of stress,and select out the anti-stress drugs with preventive and therapeutic effects,which not only has significance to human health,but also has the profound medical and social significance.Under the condition of stress,the level of corticosterone in the blood was increased,which affects the function of synaptic transmission in hippocampus,that’s leaded to the impairment of learning and memory.As a main response index of body stress,corticosterone can effectively regulate learning and memory ability of hippocampus,it also closely related to hippocampal synaptic plasticity,especially long-term depression and long-term potentiation.Resveratrol has a neuroprotective effect,which could reduce the level of oxidative stress in the brain cells,free radical damage caused by cerebral ischemia and the incidence of depression,it also can delay the occurrence of Alzheimer’s disease.ObjectiveThe aims of this study was to investigated the effect and its possible mechanism of stress on synaptic transmission in hippocampus and the regulation of resveratrol on the changes of synaptic transmission induced by stress.Methods1.Effect of different frequencies of stimulation on synaptic transmission of PP-DG pathway in hippocampus:by using electrophysiological basicⅢtransmission,long-term depression and long-term potentiation to investigate effect of different frequencies of stimulation on synaptic transmission of PP-DG pathway in hippocampus.2.Effect of corticosterone on synaptic transmission of PP-DG pathway in hippocampus:by using long-term depression,long-term potentiation and paired pulse facilitation to investigate effect of corticosterone on synaptic transmission of PP-DG pathway in hippocampus.3.mechanism of corticosterone on synaptic transmission of PP-DG pathway in hippocampus:apply N-methyl-D-aspartic acid receptor antagonist and NMDA receptor agonist to investigate mechanism of corticosterone on synaptic transmission of PP-DG pathway in hippocampus by using long-term depression and long-term potentiation.4.regulation of resveratrol on the change of synaptic transmission induced by stress:apply resveratrol to investigate regulation of resveratrol on the change of synaptic transmission induced by stress.Results1.Different frequencies of stimulation have different effects on synaptic transmission of PP-DG pathway in hippocampus.After stimulation of 1Hz 900 times,there is a phenomenon of LTD(P<0.01),after stimulation of 100Hz 100 cluster,there is a phenomenon of LTP,but no significant difference(P>0.05),after stimulation of 400Hz 100 cluster,there is a phenomenon of LTP(P<0.01).2.Damage of corticosterone on synaptic transmission of PP-DG pathway in hippocampus.Corticosterone has no significant effect on basic transmission of PP-DG pathway in hippocampus(P>0-05),corticosterone has no significant effect on paired pulse facilitation of PP-DG pathway in hippocampus(P>0.05),corticosterone has significant effect on long-term depression of PP-DG pathway in hippocampus(P<0.01),corticosterone has significant effect on long-term potentiation of PP-DG pathway in hippocampus(P<0.01).3.Damage of corticosterone on synaptic transmission of PP-DG pathway in hippocampus relate to NMDA receptor.NMDA receptor antagonist(PEAQX、TCN-201、Ifen and Ro25-6981)has significant effect on long-term depression of PP-DG pathway in hippocampus(P<0.01),NMDA receptor antagonist(D-AP5)has no significant effect on long-term depression of PP-DG pathway in hippocampus(P>0.05),NMDA receptor antagonist(D-AP5、PEAQX、TCN-201 和 Ro25-6981)has significant effect on long-term potentiation of PP-DG pathway in hippocampus(P<0.01),NMDA receptor antagonist(Ifen)has no significant effect on long-term potentiation of PP-DG pathway in hippocampus(P>0.05),NMDA receptor agonist(D-Serine)has significant effect on long-term depression and long-term potentiation of PP-DG pathway in hippocampus(P<0.01).4.Resveratrol can improve the damage of synaptic transmission of PP-DG pathway in hippocampus.Single intragastric administration of resveratrol failed to improve LTP damage of PP-DG pathway in hippocampus induced by corticosterone(P>0.05),Single intraperitoneal injection of resveratrol failed to improve LTP damage of PP-DG pathway in hippocampus induced by corticosterone(P>0.05),intragastric administration of resveratrol for 7 consecutive days can improve LTP damage of PP-DG pathway in hippocampus induced by corticosterone(P<0.01),single intracerebroventricular injection of resveratrol can improve LTD and LTP damage of PP-DG pathway in hippocampus induced by corticosterone(P<0.01).Conclusion1.Different frequencies of stimulation have different effects on synaptic transmission of PP-DG pathway in hippocampus:Low frequency suppression-high frequency enhancement;2.Corticosterone can damage synaptic transmission of PP-DG pathway in hippocampus:Low frequency enhancement-high frequency suppression;3.Corticosterone is responsible for the damage of synaptic transmission of PP-DG pathway in hippocampus by inhibiting the function of NMDA receptor;4.Resveratrol can improve the damage of synaptic transmission of PP-DG pathway in hippocampus.