Effect Of Repetitive Transeranial Magnetic Stimulation On Learning Memory And Synaptic Plasticity Of The Hippocampus In Depressed Rats

BackgroundDepression is a kind of emotional disorder caused by a variety of factors, often accompanied by the damage of cognitive function and biological aspects change. The interaction between depression and cognitive dysfunction, greatly influence the patient’s rehabilitation treatment effect and life quality. The potential of noninvasive neurostimulation by repetitive transcranial magnetic stimulation (rTMS) for improving psychiatric disorders has been studied increasingly over the past two decades. This is especially the case for major depression. In2008the FDA approved it can be used in the treatment of depression, its therapeutic action on cognitive function of depression is generally concerned by domestic and foreign scholars, but there is little knowledge about the underlying mechanisms.ObjectiveTo observe the effects of repetitive transeranial magnetic stimulation on depressive like learning and memory, the neuron and synapse ultrastructure of hippocampus CA3in chronic unpredictable mild stress rats, to detect the expression of SYP protein in hippocampus, to investigate synaptic plasticity mechanisms of rTMS on improve learning memory impairment of depressed rats.Methods1Forty SD rats were randomly divided into normal group (n=10) and model group (n=30). To establish the depression rat model by chronic unpredictable mild stress. Model group were divided into three groups (n=10):depression group, rTMS group and sham stimulation group.2Giving rTMS:3sessions of rTMS with frequency of15Hz weft given to the rTMS group, with each session including80trains with20pules of it during continuous5days. The time ofinter-session is2days. Sham stimulation group in the same environment, giving only the same number of sound stimulation without electricity and current pulse.3The sucrose water consumption test and open-field test were used to evaluate depressive like behaviors for each group. Before and after making model, and a third times, after giving rTMS, Morris water maze test, including place navigation and spatial probe test, were performed among each groups.4To detect the expression of SYP protein by Immunohistochemistry. In addition, the ultrastructures of hippocampus CA3were detected with electron microscope.Results1Making model test:There were significant differences between normal rats and depression model rats in sucrose water consumption test (t=4.807, P=0.000), horizontal behavior of open-field test (t=3.332, P=0.002), vertical behavior (t=2.845, P=0.006) and Stool frequency (t=-3.308,.P=0.003). All of them demonstrated the depression model had been established successfully.2Morris water maze test:(1) Before making model, there were no significant in the swimming speed (t=0.549, P=0.586), the average latency (t=0.334, P=0.732), the swim time in platform quadrant (t=0.989, P=0.329), the swim distance present in platform quadrant (t=0.359, P=0.724).(2) After making model, There were significant differences between normal rats and depression model rats in the average latency (F=39.707, P=0.000), the swim time in platform quadrant (F=293.727, P=0.001), the swim distance present in platform quadrant (F=249.651, P=0.000); but there were no significant differences in the swimming speed (F=0.803,P=0.501).(3) After giving rTMS, rTMS group compared with depression group and sham stimulation group, all the behavioral results without the swimming speed were statistically significant(P<0.05). And of all the behavioral results, there were no significant differences between depression group and sham stimulation group (P>0.05).3Immunohistochemical results:Positive cells integral light density of SYP in the hippocampus of control group and rTMS group are higher than rTMS group, the different have statistical significance (F=388.673, P=0.000).4Electron microscope results:That the ultrastructure of neuron and synapse in the hippocampus CA3of depression rats suffered pathological changes, and rTMS can make them improve. Synaptic morphological parameters comparison:The surface number density (F=9.521, P=0.000), Area density (F=25.853, P=0.000), volume density (F=12.066,P=0.000).Conclusions1rTMS can improve the learning and memory disorder and the expression of SYP in the hippocampus of depression rats.2That the ultrastructure of neuron and synapse in the hippocampus CA3of depression rats suffered pathological changes, and rTMS can make them improve.3rTMS can improve the learning and memory abilities, its possible mechanism is that the synaptic plasticity of the expression of SYP in hippocampal CA3region.