Fluorescence Imaging Analysis Of Cys In Depressed Mice

Depression is a mental illness with extremely complicated pathogenesis,usually showing symptoms such as negative,pessimistic,self-denial,and even suicide.The occurrence of depression can seriously disrupt the normal life of patients.With the morbidity rising year by year,the detection and treatment of depression has received continuous and widespread attention worldwide.At present,the main clinical method for diagnosing depression is to test patients with suspected depression through the Hamilton Depression Scale,the Baker Depression Scale,and the Ruskin Depression Scale.Unfortunately,these methods cannot objectively and accurately reflect whether a patient with suspected depression is suffering from the disease and the degree of remission after medication.There will also be more interfering factors in the evaluation of the efficacy of the doctor and the adjustment of the subsequent treatment plan.Therefore,it is urgent to develop a new method that can objectively and accurately monitor depression.Depression is closely related to the redox imbalance--oxidative stress in the brain.Cysteine(Cys)is an important reducing substance,and its level changes directly affect the occurrence of oxidative stress in the brain.However,due to the lack of imaging tools for highly selective recognition of Cys,the changes of Cys in the living brain during the development of depression remain unknown.Fluorescence imaging has the advantages of non-invasiveness,low cost,high sensitivity,and high spatiotemporal resolution.Therefore,we have developed an effective method for highly selective in situ fluorescence imaging of Cys,thereby revealing the relationship between the pathogenesis of depression and Cys,which will facilitate the precise monitoring of the diagnosis and treatment of depression.To solve the above problems,we first developed a two-photon fluorescent probe with high selectivity and sensitivity for real-time,in situ detection of Cys in living brains.For the first time,we achieved imaging of Cys in the brain of mice and revealed a decrease in Cys in the brain of depression mice.In order to further develop a fluorescence imaging method for the evaluation of drug efficacy in the treatment of depression,we have also designed and synthesized a near-infrared fluorescent probe with mitochondrial targeting function.Through small animal living fluorescence imaging technology,preliminary anti-antibiotic effects Evaluation of the efficacy of depression drugs.The main contents of paper are as follows:1.Based on the specific nucleophilic addition reaction of carbon-sulfur double bonds with Cys,we designed a new two-photon fluorescent probe to achieve highly selective detection of Cys.We used probes to visualize changes in endogenous Cys in cells.More importantly,using twophoton imaging technology,we successfully analyzed Cys in the brain of mice,and for the first time revealed that Cys content in the brain of depression mice was significantly lower than that of normal mice.This work confirms the important role of Cys in the brain and provides researchers with new strategies and new ways to explore the molecular mechanisms related to depression at the living level.2.We have further developed a near-infrared fluorescent probe with mitochondrial targeting.Using this probe,we observed a decrease of Cys in the brain of depression mice.In addition,we used this probe to observe different levels of Cys in the brain of depression mice treated with three antidepressants,accompanied by varying degrees of depression which is consistent with the results of our behavior analysis.Therefore,the probe can realize the diagnosis of depression and the evaluation of the efficacy of antidepressant drugs.This work provides a new method for evaluating the efficacy of depression for the precise diagnosis and prognosis of depression,which is conducive to the development of antidepressants and clinical trials at a later stage...