Metabolomic profiling relates tianeptine effectiveness with hippocampal GABA, myo-inositol, cholesterol, and fatty acid metabolism restoration in socially isolated rats.
Rationale: Discovering 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. Objectives: In this study, metabolomics was used in unraveling metabolite fluctuations of MDD and drug outcome by...
| Published in: | Psychopharmacology Vol. 239; no. 9; pp. 2955 - 2975 |
|---|---|
| Main Authors: | , , , , |
| Format: | Journal Article |
| Published: |
Springer Nature
Sep2022
|
| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=158563454&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 158563454 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00333158 EJD jtl: Psychopharmacology issn: 00333158 maglogo: N pubinfo: dt: Sep2022 vid: 239 iid: 9 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 158563454 157736111 10.1007/s00213-022-06180-y 158563454 ppf: 2955 ppct: 20 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Metabolomic profiling relates tianeptine effectiveness with hippocampal GABA, myo-inositol, cholesterol, and fatty acid metabolism restoration in socially isolated rats. aug: au: Perić, Ivana Lješević, Marija Beškoski, Vladimir Nikolić, Milan Filipović, Dragana affil: Department 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 sug: ab: Rationale: Discovering 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. Objectives: In 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−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 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 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. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|