Metabolomic profiling relates tianeptine effectiveness with hippocampal GABA, myo-inositol, cholesterol, and fatty acid metabolism restoration in socially isolated rats.

Ivana Perić, Marija Lješević, Vladimir Beškoski, Milan Nikolić, Dragana Filipović

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Article in Psychopharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers in PubMed

0.5field-weighted citation impact, top 47% of its field

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1 citing paper in PubMed, 8 citations in OpenAlex.

Current Evidence from Animal Models on Molecular Changes Underlying Antidepressant Effects of Psychobiotics.Pharmaceutics · 2026
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5 authors at 2 institutions in 1 country.

Ivana PerićDepartment of Molecular Biology and Endocrinology, "VINČA" Institute of Nuclear Sciences - National Institute of the Republic of Serbia, University of Belgrade, Mike Petrovića Alasa 12-14, 11351, Vinča, Belgrade, Serbia.

Marija LješevićInstitute of Chemistry, Technology and Metallurgy, University of Belgrade, Njegoševa 12, 11000, Belgrade, Serbia.

Vladimir BeškoskiDepartment of Biochemistry, University of Belgrade - Faculty of Chemistry, Studentski trg 12-16, 11000, Belgrade, Serbia.

Milan NikolićDepartment of Biochemistry, University of Belgrade - Faculty of Chemistry, Studentski trg 12-16, 11000, Belgrade, Serbia.

Dragana FilipovićDepartment of Molecular Biology and Endocrinology, "VINČA" Institute of Nuclear Sciences - National Institute of the Republic of Serbia, University of Belgrade, Mike Petrovića Alasa 12-14, 11351, Vinča, Belgrade, Serbia. dragana@vinca.rs.

University of Belgrade · RSUniversity of Belgrade – Faculty of Chemistry

Funding

Ministarstvo Prosvete, Nauke i Tehnološkog Razvoja 451-03-68/2022-14/ 200017Ministarstvo Prosvete, Nauke i Tehnološkog Razvoja 451-03-9/2021-14/200026Ministarstvo Prosvete, Nauke i Tehnološkog Razvoja 451-03-9/2021-14/ 200168

6 · The paper itself

Abstract

rationaleDiscovering biomarkers of major depressive disorder (MDD) can give a deeper understanding of this mood disorder and improve the ability to screen for, diagnose, and treat MDD.

objectivesIn this study, metabolomics was used in unraveling metabolite fluctuations of MDD and drug outcome by creating specific metabolomic fingerprints. 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

resultsThe 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 negative 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 effect 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 effectiveness and resilience, metabolomics revealed myo-inositol, GABA, cholesterol, and its metabolite. A significant moderate positive correlation between myo-inositol and immobility was revealed. Tian probably acted by upregulating NMDAR's and α

conclusionMetabolomics 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.

Indexed as

Major Depressive DisorderAnimalsCholesterolFatty Acidsgamma-Aminobutyric AcidHippocampusInositolMaleRatsRats, WistarThiazepinesCholesterolFatty Acidsgamma-Aminobutyric AcidInositolThiazepinestianeptineDepressionGC × GC–MSHippocampusMetabolomicsTianeptine

Identifiers

PMID35776189

DOI10.1007/s00213-022-06180-y

OpenAlexW4283743553

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.