Data_Sheet_1_Tryptophan-5-HT pathway disorder was uncovered in the olfactory bulb of a depression mice model by metabolomic analysis.docx

Major depression (MD) is a severe mental illness that creates a heavy social burden, and the potential molecular mechanisms remain largely unknown. Lots of research demonstrate that the olfactory bulb is associated with MD. Recently, gas chromatography-mass spectrometry-based metabolomic studies on depressive rats indicated that metabolisms of purine and lipids were disordered in the olfactory bulb. With various physicochemical properties and extensive concentration ranges, a single analytical technique could not completely cover all metabolites, hence it is necessary to adopt another metabolomic technique to seek new biomarkers or molecular mechanisms for depression. Therefore, we adopted a liquid chromatography-mass spectrometry metabonomic technique in the chronic mild stress (CMS) model to investigate significant metabolic changes in the olfactory bulb of the mice. We discovered and identified 16 differential metabolites in the olfactory bulb of the CMS treatments. Metabolic pathway analysis by MetaboAnalyst 5.0 was generated according to the differential metabolites, which indicated that the tryptophan metabolism pathway was the core pathogenesis in the olfactory bulb of the CMS depression model. Further, the expressions of tryptophan hydroxylase (TpH) and aromatic amino acid decarboxylase (AAAD) were detected by western blotting and immunofluorescence staining. The expression of TpH was increased after CMS treatment, and the level of AAAD was unaltered. These results revealed that abnormal metabolism of the tryptophan pathway in the olfactory bulb mediated the occurrence of MD.

重度抑郁症（Major Depression, MD）是一种造成沉重社会负担的严重精神疾病，其潜在分子机制目前尚未完全阐明。多项研究表明，嗅球（olfactory bulb）与重度抑郁症存在关联。近期，针对抑郁模型大鼠的基于气相色谱-质谱联用（gas chromatography-mass spectrometry, GC-MS）的代谢组学研究显示，嗅球内嘌呤与脂质代谢出现紊乱。由于代谢物具有多样的理化性质且浓度跨度极大，单一分析技术无法完全覆盖所有代谢物，因此有必要采用另一类代谢组学技术，以探寻抑郁症的新型生物标志物或潜在分子机制。因此，本研究采用液相色谱-质谱联用（liquid chromatography-mass spectrometry, LC-MS）代谢组学技术，以慢性轻度应激（chronic mild stress, CMS）小鼠模型为对象，探究其嗅球内的显著代谢变化。本研究在CMS模型小鼠的嗅球中发现并鉴定出16种差异代谢物。基于上述差异代谢物，研究人员利用MetaboAnalyst 5.0开展代谢通路分析，结果表明色氨酸代谢通路是CMS抑郁模型小鼠嗅球中的核心致病通路。此外，本研究通过蛋白质免疫印迹（Western Blotting, WB）与免疫荧光染色技术，检测了色氨酸羟化酶（tryptophan hydroxylase, TpH）与芳香族氨基酸脱羧酶（aromatic amino acid decarboxylase, AAAD）的表达水平。CMS造模后，小鼠嗅球内TpH的表达水平显著上调，而AAAD的表达水平无明显变化。上述结果表明，嗅球内色氨酸代谢通路异常介导了重度抑郁症的发生。