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The Systematic Review, Meta-Analysis and Proteomics Study on Major Depression Assessing the Effect of Acute Tryptophan Depletion

Author: WangJiaJia
Tutor: XiePeng
School: Chongqing Medical University
Course: Neurology
Keywords: Depression Rapid tryptophan depletion System Evaluation Meta-analysis Proteomics Hippocampal
CLC: R749.4
Type: Master's thesis
Year: 2011
Downloads: 60
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Abstract

Background According to the statistics of the World Health Organization in 2000, depression in the global incidence of approximately 11%. Incidence of about 3% to 5%. In stark contrast with the high incidence of Grade three hospitals, non-psychiatrist identification of depression only 21%. In contradiction of the low recognition rate and the high incidence because clinical depression diagnosis depends on the subjective judgment of the lack of reliable laboratory diagnostic indicators. Therefore, the understanding of the pathogenesis of depression, looking for possible laboratory diagnosis is based on the main direction for depression research. The purpose of this project is to comply with converted Medical (Translational medicine) ideas, combining clinical and basic research. Systematic reviews and Meta analysis of studies using SSRIs antidepressant medication in patients with depression after rapid tryptophan depletion mood and sleep EEG changes; cause mood and sleep EEG Subsequently, according to their results concern change is closely related to 5-HT can the system function, the production of the corresponding animal model; Finally, the use of proteomics research methods to study the differences in 5-HT energy systems function brain regions - the hippocampus expressed proteins, in order reveal organic brain associated with the pathogenesis of depression Metabolic Basis of done a useful exploration method for the laboratory diagnosis of depression. This experiment is divided into three parts: the first part of the system of rapid tryptophan depletion test (Tryptophan depletion, TD) SSRIs medications in patients with depression, mood and sleep EEG impact evaluation and Meta-analysis; animal model of rapid tryptophan depletion; Part III rapid tryptophan depletion rat models of brain proteomics research. Main methods and technology roadmap: The system can search at home and abroad have been published on the use of the SSRIs antidepressant drugs depression patients the TD trial of high-quality RCT study of literature was, according to the Jadad standard quality analysis and Meta-analysis using RevMan 4.2 system can not merge data evaluation. Male Sprague-Dawley adult rats 30 behavioral screening randomly divided into rapid tryptophan depletion group, the gelatin control group and the saline control group. After two weeks of adaptability gavage, sub-irrigation with a neutral amino acid mixture without tryptophan, making rapid tryptophan depletion animal model. 5-7 hours after administration line the sucrose water consumption test (Sugar water consumption test, SWCT), the wilderness trials (Open field test, and OFT). According to the results of systematic reviews and meta-analysis, selection and 5 - serotonergic system function is closely related to the hippocampus, in accordance with the requirements of the proteomics sample preparation, extracted with trichloroacetic acid - acetone precipitation (TCA-acetone precipitation method) hippocampal tissue protein Bradford assay protein concentration, protein spots separated by two-dimensional gel electrophoresis (2-DE), stained with Coomassie blue and silver staining. Application PDQuest 8.2 image analysis system for analysis of differential protein spots, and sequence analysis of the protein spots using LC-MS/MS technology. The resulting data in the the NCBInr database retrieval, identification of protein function. Differences in protein and validated by RT-PCR and Western blot (Western Blot). The results of the literature search, the final total into the two high-quality clinical RCT literature (impact factor of 12.257 and 6.993, respectively), the Jadad score 3 points and 4 points. System evaluation results show that TD clinical trials, the experimental group, total plasma tryptophan and free tryptophan concentration content significantly reduce the lower valley eight hours after the first dose, 16 hours after gradually restored to normal levels. The fast tryptophan depletion after five hours, experimental rats syrup consumption degree of decline in the percentage decreased horizontal movement distance and the average speed of movement, there is a significant difference (P lt; 0.05) compared with the control group. The hippocampus two-dimensional gel electrophoresis protein spots are an average of 1000 ± 20 points, 2-DE gels in the group match was 69%, a total of 67 protein spots exist in the amount of significant differences between the groups (pairwise comparisons among the three groups in parallel t test, P lt; 0.05), the point of difference is focused on of pH4.0 ~~ 9.0 molecular weight is concentrated in 20 to 75 KD. Conclusions TD trial to influence by the SSRIs after the drug treatment of depression in patients with plasma tryptophan levels and cause mood changes and emotional changes mainly in the two emotions of depression and confusion. TD test induced depression in patients with rapid eye movement latencies shortened the fast increase in the proportion of REM, rapid eye movement eye movement increasing frequency during the changes in the sleep cycle. TD model animals showed short-term depression: decreased interest, decreased activity, anorgasmia and clinical manifestations of human depression, can be used as one of the studies in animal models of depression.

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