Metabolomics Study Of Olfactory Bulb Among CUMS Rat Model Of Depression

Background:Depression is a common mental illness, the striking and lastingdepressed mood as the main clinical features. Moreover, the Morbidity andmortality associated with depression, to patients, families and society hasbrought the families and society a heavy burden, nevertheless itspathogenesis is unclear yet.Objective:Prior evidences among Chronical Unpredictable Mild Stress(CUMS)rat model of depression showed the functional and structuralabnormalities of the olfactory bulb of patients with depression amongdepression patients; while bilateral olfactory bulb removal of the rat hasbecome a wide spread depression animal models. A preliminary study fromour group had unraveled proliferation of neural stem cell decreased in thesubventricular zone (SVZ) as well as the neural precursor cells and matureneurons presented significantly downregulated coupled wiht increasedapoptosis accompanied by the dysfunction on presynaptic membrane, also,reduced volume and dysfunction of the olfactory bulb. In addition, the data(unpublished data) from proteomics study group in our group suggestthat the olfactory bulb of the rat model of depression enzyme related proteinsof the olfactory bulb among the rat model of depression have been changed.Therefore, the olfactory bulb has been widespread concerned to underlie thepathophysiology of depression.Methods:20healthy male SD rats were randomly divided into the CUMS group(10) and normal group (10), all rats were subjected exposed to a four-weekCMS procedure, whereas control rats were left undisturbed. At the end ofevery week, the sucrose preference was applied to test the anhedonia. In thelast week, the open field test and forced swimming test was performed.Using a gas chromotography/mass spectrometry (GC/MS) metabolomicapproach,The olfactory bulb of CUMS model based on the GC/MSmetabolomics profiling analysis, multivariate statistical analysis (PCA,PLS-DA, OPLS-DA) has access to obtain the different metabolites related torat model of depression, clustering them by their function, analyzing the databy their metabolic pathway.Results:Following three weeks of stress exposure, sucrose preference wassignificantly decreased in the anhedonic group as compared to the controlgroups. CUMS rats presented the changes in body weight, open field testand, in all likelihood, which were statistically different from control rats. Hence, the CUMS rat model of depression was successfullyestablished.Using a gas chromotography/mass spectrometry (GC/MS)metabolomic approach,The olfactory bulb of CUMS model based on the GC/MS metabolomics profiling analysis, the data were significantly separatedby multivariate statistical analysis (PCA, PLS-DA, OPLS-DA). Finally,19differential metabolites were ruled out.13out of them were downregulated,they are Dehydroascorbate the arachidonic acid, docosahexaenoic acid(DHA), oleic acid,24three-carbon acid, glycolic acid, ribitol, acetyl asparticacid, cysteine sulfinic acid, guanosine, inosine; While6out of them wereupregulated, they are glycerol phosphate chain sterol (dehydrocholesterol)campesterol, sitosterol, inositol phospholipid, glyceric acid. Thesemetabolites reported are pertinent mainly with energymetabolism(glycolysis metabolism and lipid metabolism) and nucleotidemetabolism.Conclusion:The differential metabolites from olfactory bulb of CUMS rat model ofdepression present mainly on the lipid metabolism and glycolysismetabolism and and nucleotide metabolism which might be responsible forthe Changes of OB among rat model of depression.