Study On The Changes Of Taurine In The Brain Of Depressed Mice And Its Antidepressant Mechanisms

Depression,also known as depressive disorder,is a very common chronic persistent disease.It is characterized by marked and persistent low spirits,reduced pleasure,and reduced speech and behavior.There are more than 300 million patients worldwide,with a growth rate of about 18 % in the past decade.Different from other short-term negative emotional reactions to daily life,especially the long-term patients with moderate or severe depression may greatly affect their performance in learning and work and produce serious physical and mental reactions.However,people have not fully understood the pathological mechanism of depression.It is generally believed that depression is a mood disorder caused by a variety of factors,and the treatment effect of depression is not very satisfactory.Generally,it takes more than two weeks for treatment to be effective and the treatment drugs are expensive,with high recurrence rate and many side effects,which brings heavy physical and mental burden to patients and their families.Therefore,finding drugs with fewer side effects and cheaper prices has become an urgent task in current depression research.As a kind of mental disease,the changes of various metabolites in the brain are the end products in the process of depression occurrence and development.The changes of the types and quantities of metabolites can be regarded as the final reflection of the brain to the stimulation of gene or environmental inflammation changes,which has a more direct relationship with the changes of related emotions of the organism.We found that the concentration of taurine in the brain decreased significantly in depression through preliminary experimental screening and related literature,and taurine supplementation can improve depression symptoms.Taurine is a kind of semi essential amino acid widely used in our life It is one of the most abundant amino acids in human body,which is very important to human body.It has been reported that taurine can regulate immune inflammatory reaction,promote nerve growth,antagonize endoplasmic reticulum stress,regulate gene expression,antioxidation,regulate calcium balance,regulate cell osmotic pressure and so on.In view of the above findings,it is reasonable to believe that taurine plays an important role in the process of depression.Taurine or its derivatives may become new antidepressants.In this study,the chronic social defeat stress(CSDS)model of mice is the main research object.This paper mainly studies the interaction between taurine and depression like behavior of mice,and investigates the influence of taurine on brain structure and function in depressed mice.That is,to reveal the role of taurine in depression from the structure and function,so as to provide new ideas for the treatment of depression,promote the development of new antidepressant drugs.Part Ⅰ Change of taurine in the brain of mice with chronic social frustration stress depression and its antidepressant effectObjective: To establish a mouse model of chronic social frustration stress,to detect changes in taurine in the brain of a mouse model of chronic social frustration stress,and to observe the effect of taurine supplementation on depression-like behavior in mice.Methods: A chronic social defeat stress(CSDS)mice model was established,and a series of behavioral experiments including social interaction test(SIT),sucrose preference test(SPT)and forced swimming test(FST)were used to detect the animal models;Metabolomics was used to detect the metabolic substances in the brain of mice with depression phenotype and control group.Taurine content in the brain of mice was quantified by taurine assay kit and immunohistochemistry.The changes of depression-like behaviors in mice were observed after intraperitoneal taurine injection.Results:1.Compared with the normal control mice,the social ratio decreased in the social interaction test(P < 0.001),the sucrose consumption rate decreased in the sucrose preference test(P < 0.01),and the immobility time prolonged in the forced swimming test(P < 0.001);2.Compared with the normal control mice,m PFC metabolism group of chronic social defeat stress mice showed significant changes(P < 0.05);3.Taurine assay kit and immunofluorescence staining showed that taurine content in m PFC decreased in the chronic social defeat stress model(P < 0.05);4.Compared with the mice without taurine,Taurine supplementation could increase the social rate(P < 0.05)and the immobility time decreased(P < 0.05)in the forced swimming experiment,but there was no statistical difference in the sugar water consumption rate in the sucrose preference test.Conclusion:1.Chronic social defeat stress can cause depression like behaviors in mice,which can be used as an ideal animal model of depression;2.Chronic social defeat stress can reduce taurine content in m PFC,taurine supplementation can inhibit depression like behavior.Part Ⅱ Exploration of the mechanism of taurine exerting antidepressant effectObjective: To explore the causes of taurine changes and the effects of taurine supplementation on mice brain by chronic social defeat stress model of mice.Methods: Western blot method was used to detect the expression of taurine synthesis and transport related protein,glutamate metabolism related protein and synaptic plasticity related protein PSD 95 and Syn 1a in the m PFC of chronic social defeat stress mice.Immunofluorescence staining was used to detect the NR 2A expression in the m PFC.Observing the changes of calcium activity level of astrocytes through taurine competitive inhibitor β-alanine.Taurine content in m PFC of chronic social defeat stress mice after taurine was evaluated by taurine assay kit and immunofluorescence;The changes of taurine and NR 2A in m PFC of mice were evaluated by western-blot and immunofluorescence.Results:1.Chronic social defeat stress had no effect on the expression of taurine synthesis and transport related proteins in m PFC,while the expression of NR 2A and syn1 a were reduced in m PFC.2.When β-alanine,a taurine competitive inhibitor,was added to astrocytes,the calcium activity of astrocytes decreased and the incubation period increased;3.Taurine supplementation could increase the content of taurine and the expression of NR 2A in m PFC of mice with chronic social defeat stress(P < 0.01);4.The structural plasticity of neurons in the m PFC of depressed mice with chronic social frustration stress was changed,and taurine supplementation could reverse the changes of neurons in the m PFC of depressed mice;The density of dendritic spines in the m PFC of depressed mice with chronic social frustration stress decreased,and taurine supplementation could improve the density of dendritic spines in the m PFC of depressed mice.Conclusion:The expression of taurine synthesis and transport-related proteins in m PFC was not involved in the regulation of depression,however,the expressions of synaptic plasticity protein Syn 1A and NMDA receptor NR 2A were changed,the plasticity of neurons was decreased,and the density of dendritic spines was decreased.Taurine supplementation can increase the expression of NR 2A in m PFC of mice,improve the plasticity of neurons in m PFC of mice,and improve the density of dendritic spines.