Metabolomic profiling relates tianeptine effectiveness with hippocampal GABA, myo-inositol, cholesterol, and fatty acid metabolism restoration in socially isolated rats
| العنوان: | Metabolomic profiling relates tianeptine effectiveness with hippocampal GABA, myo-inositol, cholesterol, and fatty acid metabolism restoration in socially isolated rats |
|---|---|
| المؤلفون: | Ivana Perić, Marija Lješević, Vladimir Beškoski, Milan Nikolić, Dragana Filipović |
| المصدر: | Psychopharmacology |
| بيانات النشر: | Springer Science and Business Media LLC, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Male, Pharmacology, Depressive Disorder, Major, Thiazepines, Depression, Fatty Acids, GC×GC–MS, Hippocampus, Rats, Cholesterol, GC × GC–MS, Animals, Metabolomics, Rats, Wistar, Tianeptine, Inositol, gamma-Aminobutyric Acid |
| الوصف: | Rationale: Discovering biomarkers of major depressive disorder (MDD) can give a deeper understanding of this mood dis order and improve the ability to screen for, diagnose, and treat MDD. Objectives: In this study, metabolomics was used in unraveling metabolite fuctuations of MDD and drug outcome by creating specifc metabolomic fngerprints. We report metabolomic patterns of change of the hippocampus of adult male Wistar rats following chronic social isolation (CSIS) (6 weeks), an animal model of depression, and/or chronic tianeptine (Tian) treatment (10 mg kg−1 per day) (lasting 3 weeks of 6-week CSIS), monitored by using comprehensive GC×GC–MS. Results: The comparative metabolomic analysis highlighted the role of gamma aminobutyric acid (GABA), iso-allocholate, and unsaturated fatty acid metabolism alterations following the CSIS, which was corroborated with moderate to strong nega tive Pearson’s correlation of GABA, docosahexaenoic, 9-hexadecenoic acid, 5,8,11,14-eicosatetraynoic, and arachidonic acids with immobility behavior in the forced swim test. The antidepressant efect of Tian restored GABA levels, which was absent in Tian resilient rats. Tian decreased myo-inositol and increased TCA cycle intermediates, amino acids, and cholesterol and its metabolite. As key molecules of divergence between Tian efectiveness and resilience, metabolomics revealed myo-inositol, GABA, cholesterol, and its metabolite. A signifcant moderate positive correlation between myo-inositol and immobility was revealed. Tian probably acted by upregulating NMDAR’s and α2 adrenergic receptors (AR) or norepinephrine transporter in both control and stressed animals. Conclusion: Metabolomics revealed several dysregulations underlying CSIS-induced depressive-like behavior and responsiveness to Tian, predominantly converging into NMDAR-mediated glutamate and myo-inositol signalization and GABA inhibitory pathways. |
| تدمد: | 1432-2072 0033-3158 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::410c98ac3673a267817650dc25b24877Test https://doi.org/10.1007/s00213-022-06180-yTest |
| حقوق: | RESTRICTED |
| رقم الانضمام: | edsair.doi.dedup.....410c98ac3673a267817650dc25b24877 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14322072 00333158 |
|---|