Mechanism On The Behavior And Hippocampal Neuroplasticity In Model Rats Of Depressed Post-MI With Electro-acupuncture

AIMTo observe the effects on the change of behavior and hippocampal neurone in model rats of depressed post-MI with electro-acupuncture. And to investigate the measure on model rats of depressed post-MI,in accord with the mechanism on post-MI depression and treatment with electro-acupunctureMETHODS1.All adult male Sprague-Dawley rats were divided into four groups randomly including normal control group,sham operated group,model group,electro-acupuncture(EA) group and fluoxetine(FXT)group.The model was established with the measure of chronic stress depression and singly housed in 21 days after acute myocardial infarction.2.The behaviors of rats have been detected by open-field test and sucrose preference test on the beginning,the 7th,the 14th and the 21 st day by treated with EA.3.TUNEL method was used to measure the hippocampal apoptosis.4.Immunohistochemistry method was used to measure the expression of Bcl-2 and Bax in the hippocampus.5.The contents of BDNF,P-CREB and p-ERK protein expression in rat hippocampus were investigated with Western-blot technique.6.The contents of BDNFmRNA,CREBmRNA and ERK1/2mRNA expression in rat hippocampus were investigated with RT-PCR technique.RESULTS1.Compared with normal control group,rats in model group,which were exposed to chronic unpredicted mild stressors and were singly housed after 21 days in accordance with decreased weight and fluid intake significantly.And the behavior of model rats including reduced Squaresc rossed,rears,grooming and increased central time stopped in open-field test were observed.It also showed that a significant reduction of consumption of sucrose solutions,and an increased pure water.(p＜0.05).It suggested that chronic stress could affect weight and behavior of rats.After 3 weeks of antidepressant treatment,all the records of the behavioral testing of the rats in EA and FTX groups have significantly improved(p＜0.05).It suggested that both EA and FXT could improve body weight and behavior of depressive rats.2.The positive cells in the CA3 and dentate gyrus subregion of hippocampus were observed with the TUNEL.But,the positive cells were not observed in the CA1 subregion of hippocampus.Compared to the normal group,the positive cells were increased in the model group (P＜0.05),while the positive cells were decreased in the EA and FXT group compared to the model group(P＜0.05).And there weren't difference between the EA group and FXT group(P＞0.05).3.The positive cells in the CA3 and dentate gyrus subregion of hippocampus were observed with the inununohistochemistry method.But, the positive cells were not observed in the CA1 subregion of hippocampus.Compared to the normal group,the Bax protein was increased in the model group(P＜0.05)in accord with decreased in Bcl-2 protein and Bcl-2/Bax(P＜0.05).But,compared to the model group,the decreased Bax protein and increased Bcl-2 protein,Bcl-2/Bax in the EA and FXT group(P＜0.05).And there weren't significant difference between the EA group and FXT group(P＞0.05) 4.The observation of Western-blot showed that the contents of BDNF,P-CREB和p-ERK1/2 protein expression in hippocampus of rats in depression model group were significantly decreased compared to control group(P＜0.05).While,the contents of BDNF,P-CREB和p-ERK1/2 protein expression in hippocampus of rats were increased in EA and FXT group(P＜0.05) in accordance with no significant difference between EA group and FXT group(P＞0.05)5.The observation of RT-PCR showed that the expression of BDNFmRNA,CREBmRNA and ERK1/2mRNAin hippocampus of rats in depression model group were significantly decreased compared to control group(P＜0.05).While,the expression of BDNFmRNA, CREBmRNA and ERK1/2mRNA were increased in EA and FXT group(P＜0.05).There weren't significant difference between the EA group and FXT group(P＞0.05)CONCLUSION1.The model of depressed post-MI in rat could be established successfully with chronic unpredicted mild stressors after AMI,which own the feature of MI and depression in accordance with the standard of evaluation in animal model of depression.The reproducibility of this model is safe which the symptom of depression is stable and exist in longer time.It provides a possible measure on the psychophysiological disorder to research.2.It suggested that treatment of EA couldn't affect weight and behavior of model rats in a week.After 3 weeks of antidepressant treatment,all the records of the behavioral testing in rats with EA were improved significantly.It showed that treatment of EA could improve weight and behavior of depressive rats in 3 weeks.3.The positive cells in the CA3 and dentate gyrus subregion of hippocampus were observed in the model rats in accordance with the increased Bax protein and decreased Bcl-2 protein and Bcl-2/Bax. But,there were opposite phenomenon in the EA group.It suggested that neuron apoptosis of hippocampus was related to the depression after MI.Treatment of EA could protect the hippocampus neuron by reducing the neuron apoptosis.4.The decreased BDNF and P-CREB in hippocampus of model rats showed that the depressed post-MI maybe related to the disfunction in hippocampus neurone.The BDNF and P-CREB could be increased in 3 weeks,which was the possible mechanism on the treatment with EA to resist depression and protect the hippocampus neurone.5.The decreased p-ERK1/2 in hippocampus of model rats suggested that there was the abnormal signal pathway in the post-MI depression. The treatment with EA in 3 weeks could play a role in acting on the ERK1/2 signal pathway through the key factors.