Escitalopram Targets Oxidative Stress, Caspase-3, BDNF and MeCP2 in the Hippocampus and Frontal Cortex of a Rat Model of Depression Induced by Chronic Unpredictable Mild Stress.

Dionisie, Vlad; Ciobanu, Adela Magdalena; Toma, Vlad Alexandru; Manea, Mihnea Costin; Baldea, Ioana; Olteanu, Diana; Sevastre-Berghian, Alexandra; Clichici, Simona; Manea, Mirela; Riga, Sorin; Filip, Gabriela Adriana

doi:10.3390/ijms22147483

Cited by 78Treatment of Major DepressionTryptophan and brain disordersNeurotransmitter Receptor Influence on Behavior

Escitalopram Targets Oxidative Stress, Caspase-3, BDNF and MeCP2 in the Hippocampus and Frontal Cortex of a Rat Model of Depression Induced by Chronic Unpredictable Mild Stress.

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Dionisie, Vlad, Ciobanu, Adela Magdalena, Toma, Vlad Alexandru, Manea, Mihnea Costin, Baldea, Ioana, Olteanu, Diana, Sevastre-Berghian, Alexandra, Clichici, Simona +3 more·2021·International Journal of Molecular Sciences

DOI 10.3390/ijms22147483PMC PMC8304451

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Abstract

In recent years, escitalopram (ESC) has been suggested to have different mechanisms of action beyond its well known selective serotonin reuptake inhibition. The aim of this study is to investigate the effects of escitalopram on oxidative stress, apoptosis, brain-derived neurotrophic factor (BDNF), Methyl-CpG-binding protein 2 (MeCP2), and oligodendrocytes number in the brain of chronic unpredictable mild stress-induced depressed rats. The animals were randomised in four groups (8 in each group): control, stress, stress + ESC 5 and stress + ESC 5/10. ESC was administered for 42 days in a fixed dose (5 mg/kg b.w.) or in an up-titration regimen (21 days ESC 5 mg/kg b.w. then 21 days ESC 10 mg/kg b.w.). Sucrose preference test (SPT) and elevated plus maze (EPM) were also performed. ESC improved the percentage of sucrose preference, locomotion and anxiety. ESC5/10 reduced the oxidative damage in the hippocampus and improved the antioxidant defence in the hippocampus and frontal lobe. ESC5/10 lowered caspase 3 activity in the hippocampus. Escitalopram had a modulatory effect on BDNF and the number of oligodendrocytes in the hippocampus and frontal lobe and also improved the MeCP2 expressions. The results confirm the multiple pathways implicated in the pathogenesis of depression and suggest that escitalopram exerts an antidepressant effect via different intricate mechanisms.

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Common antidepressants such as escitalopram and fluoxetine improve central function by increasing central serotonergic nerve activity and can regulate levels of brain-derived neurotrophic factors and inflammatory factors in patients' blood.
“Common antidepressants, such as escitalopram and fluoxetine, have been shown to improve central function by increasing central serotonergic nerve activity. It can also successfully regulate the levels of brain-derived neurotrophic factors and inflammatory factors in patients’ blood [25].”
From Effective biomarkers and therapeutic targets of nerve-immunity interaction in the treatment of depression: an integrated investigation of the miRNA-mRNA regulatory networks (2022) · cites this paper as [25]

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miR-16 and Fluoxetine Both Reverse Autophagic and Apoptotic Change in Chronic Unpredictable Mild Stress Model Rats
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Authors: Dionisie, V., Ciobanu, A. M., Toma, V. A., Manea, M. C., Baldea, I., Olteanu, D., Sevastre-Berghian, A., Clichici, S., Manea, M., Riga, S., & Filip, G. A.
Affiliations: Carol Davila University of Medicine and Pharmacy (RO)
Babeș-Bolyai University (RO)
Department of Physiology, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania
Iuliu Hațieganu University of Medicine and Pharmacy (RO)
Spitalul Clinic de Psihiatrie Alexandru Obregia (RO)
Corresponding author: Toma, Vlad Alexandru
Manea, Mihnea Costin
ORCID: Dionisie, Vlad
Ciobanu, Adela Magdalena
Toma, Vlad Alexandru
Manea, Mihnea Costin
Olteanu, Diana
Clichici, Simona
Filip, Gabriela Adriana
Venue: International Journal of Molecular Sciences
Publisher: MDPI AG
Published: 2021-07-13
Volume: 22
Issue: 14
Pages: 7483
ISSN: 1422-0067 (ISSN-L)
DOI: 10.3390/ijms22147483
PMC: PMC8304451
OpenAlex: W3180558542
Cited by: 78
References: 139
Citations by year: 2026: 21 · 2025: 16 · 2024: 12 · 2023: 9 · 2022: 19 · 2021: 1
FWCI: 5.99
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: International Journal of Molecular Sciences (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics: Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords: escitalopram, depression, chronic unpredictable mild stress, oxidative stress, caspase-3, apoptosis, brain-derived neurotrophic factor, MeCP2, oligodendrocytes, hippocampus, frontal cortex, antidepressant mechanism, selective serotonin reuptake inhibitors, anxiety, sucrose preference
MeSH terms: Animals, Behavior, Animal, Depression, Disease Models, Animal, Frontal Lobe, Hippocampus, Male, Stress, Psychological, Citalopram, Rats, Wistar, Oxidative Stress, Antidepressive Agents, Second-Generation, Brain-Derived Neurotrophic Factor, Rats, Methyl-CpG-Binding Protein 2, Caspase 3

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Escitalopram Targets Oxidative Stress, Caspase-3, BDNF and MeCP2 in the Hippocampus and Frontal Cortex of a Rat Model of Depression Induced by Chronic Unpredictable Mild Stress.

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