Vortioxetine mitigates neuronal damage by restricting PERK/eIF2α/ATF4/CHOP signaling pathway in rats subjected to focal cerebral ischemia-reperfusion

Emam, Amr M.; Saad, Marina; Ahmed, Naglaa A.; Zaki, Hala F.

doi:10.1016/j.lfs.2021.119865

Cited by 12 publications

(2 citation statements)

References 35 publications

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“…Vortioxetine has also been suggested to be a neuroprotective agent against neuronal damage, as it was found to restrict the PERK/eIF2alpha/ATF4/CHOP stress signalling pathway, which in rats subjected to focal cerebral ischaemia-reperfusion is involved in focal cerebral ischaemia-reperfusion-related damage [ 36 ].…”

Section: Methodsmentioning

confidence: 99%

Differential Response to Three Antidepressants in Patients with Major Depressive Episode Who Suffered Covid-19-Related Trauma

Filippis¹,

Lombardozzi

Matrone³

et al. 2022

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Background: The Covid 19 pandemic might have impacted response to drug treatment in major depressive episode (MDE). We compared responses to three different antidepressant drugs, i.e., vortioxetine, sertraline, and trazodone, in outpatients with MDE during Major Depressive Disorder (MDD), Bipolar Disorder (BD), or schizophrenia and related psychoses (SSOPDs) during two time periods, i.e., prior to suffering Covid-19–related trauma and after suffering such trauma. Methods: We conducted an observational study on clinically stabilised for at least 6 months outpatients with MDE during the course of MDD (N=58), BD (N=33), or SSOPDs (N=51). Patients, whose baseline assessments of Montgomery-Åsberg Rating Scale (MADRS), Hamilton Anxiety Rating Scale (Ham-A), Brief Psychiatric Rating Scale (BPRS), Visual Analogue Scale for Craving (VAS-crav) and World Health Organization Quality of Life, Brief version (WHOQOL-BREF) were available, were recruited at the time they suffered Covid-19–related traumas. Fifty patients, prior to the pandemic, when they were clinically stable, were treated with 15 mg/die vortioxetine, 44 with 450 mg/die trazodone, and 48 with 150 mg/die sertraline. After experiencing a major Covid-19–related personal trauma, patients showed clinical worsening which required dosage adjustment (20 mg/day vortioxetine; 600 mg/day trazodone, and 200 mg/day sertraline) and, for a part of them, a month of hospitalisation. Scores on the MADRS, Ham-A, BPRS, VAS-crav and WHOQOL-BREF were compared drug-wise and gender-wise with Student’s t test for continuous variables and χ2 for categorical variables. Result: The sample consisted of 142 outpatients (age, mean 39.63 ± 16.84; 70 men and 72 women); women were older than men (mean age 43.18 ± 17.61 vs. 35.98 ± 15.30; p=0.01). The two genders did not differ on other variables). For all treatments, symptoms worsening was observed at the time of trauma, followed by slow recovery with treatment readjustment. Trauma-related worsening in patients on vortioxetine was less intense than patients on the other two antidepressants and recovery was faster. All drugs were associated with an improvement in QoL. The vortioxetine group showed a lower hospitalisation rate (24%) than sertraline (35.4%) and trazodone (38.6%), but this was not significant (p=0.27). Conclusion: All drugs improved symptoms after Covid-19 trauma in patients with MDE, with vortioxetine showing a small advantage. No differences between vortioxetine, sertraline and trazodone were found as concerns the need for hospitalisation.

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Section: Methodsmentioning

confidence: 99%

Differential Response to Three Antidepressants in Patients with Major Depressive Episode Who Suffered Covid-19-Related Trauma

Filippis¹,

Lombardozzi

Matrone³

et al. 2022

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“…3H). Some transcription factors, such as ATF4 and BHLHE40, have been found to regulate the autophagy pathway and are associated with the pathological mechanism of MDD [49][50][51].…”

Section: Autophagy Pathway Inhibition In Astrocytes May Be Associated...mentioning

confidence: 99%

Does decreased autophagy and dysregulation of LC3A in astrocytes play a role in major depressive disorder?

He,

Shi,

et al. 2023

Transl Psychiatry

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Astrocytic dysfunction contributes to the molecular pathogenesis of major depressive disorder (MDD). However, the astrocytic subtype that mainly contributes to MDD etiology and whether dysregulated autophagy in astrocytes is associated with MDD remain unknown. Using a single-nucleus RNA sequencing (snRNA-seq) atlas, three astrocyte subtypes were identified in MDD, while C2 State-1Q astrocytes showed aberrant changes in both cell proportion and most differentially expressed genes compared with other subtypes. Moreover, autophagy pathways were commonly inhibited in astrocytes in the prefrontal cortices (PFCs) of patients with MDD, especially in C2 State-1Q astrocytes. Furthermore, by integrating snRNA-seq and bulk transcriptomic data, we found significant reductions in LC3A expression levels in the PFC region of CUMS-induced depressed mice, as well as in postmortem PFC tissues and peripheral blood samples from patients with MDD. These results were further validated by qPCR using whole-blood samples from patients with MDD and healthy controls. Finally, LC3A expression in the whole blood of patients with MDD was negatively associated with the severity of depressive symptoms. Overall, our results underscore autophagy inhibition in PFC astrocytes as a common molecular characteristic in MDD and might reveal a novel potential diagnostic marker LC3A.

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Potential Role of Endoplasmic Reticulum Stress in Modulating Protein Homeostasis in Oligodendrocytes to Improve White Matter Injury in Preterm Infants

Liu,

2024

Mol Neurobiol

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Vortioxetine mitigates neuronal damage by restricting PERK/eIF2α/ATF4/CHOP signaling pathway in rats subjected to focal cerebral ischemia-reperfusion

Cited by 12 publications

References 35 publications

Differential Response to Three Antidepressants in Patients with Major Depressive Episode Who Suffered Covid-19-Related Trauma

Differential Response to Three Antidepressants in Patients with Major Depressive Episode Who Suffered Covid-19-Related Trauma

Does decreased autophagy and dysregulation of LC3A in astrocytes play a role in major depressive disorder?

Potential Role of Endoplasmic Reticulum Stress in Modulating Protein Homeostasis in Oligodendrocytes to Improve White Matter Injury in Preterm Infants

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