ArticleJournal of neuroinflammation2022
Agomelatine rescues lipopolysaccharide-induced neural injury and depression-like behaviors via suppression of the Gαi-2-PKA-ASK1 signaling pathway.
Article in Journal of neuroinflammation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 35 citations in OpenAlex.
- Agomelatine as adjunctive therapy with SSRIs or SNRIs for major depressive disorder: a multicentre, double-blind, randomized, placebo-controlled trial.BMC medicine · 2025Trial
- CircADAM9 activates autophagy via miR-302b-3p/ULK1 axis to improve depressive-like behaviors.Biology direct · 2026Article
- Gut microbiota, circadian rhythms and their interactions: implications for the pathogenesis and treatment of depression.Annals of medicine · 2025Review
- α-synuclein in Parkinson's disease: a central point of convergence with depression.NPJ Parkinson's disease · 2025Review
- Importance of additional behavioral observation in psychopharmacology: a case study on agomelatine's effects on feedback sensitivity in probabilistic reversal learning in rats.Psychopharmacology · 2025Article
- Agonism of MTNeurochemical research · 2025Article
- Agomelatine Alleviates Depressive-like Behaviors by Suppressing Hippocampal Oxidative Stress in the Chronic Social Defeat Stress Model.Antioxidants (Basel, Switzerland) · 2025Article
- Modulation of autophagy by melatonin and its receptors: implications in brain disorders.Acta pharmacologica Sinica · 2025Review
- Behavioural and neurochemical alterations following acute inflammation induced by intraperitoneal and intratracheal injection with lipopolysaccharide in mice.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- The antidepressant effects of kaji-ichigoside F1 via activating PPAR-γ/CX3CR1/Nrf2 signaling and suppressing NF-κB/NLRP3 signaling pathways.Frontiers in pharmacology · 2025Article
- Levomilnacipran Improves Lipopolysaccharide-Induced Dysregulation of Synaptic Plasticity and Depression-Like Behaviors via Activating BDNF/TrkB Mediated PI3K/Akt/mTOR Signaling Pathway.Molecular neurobiology · 2024Article
- Agomelatine improves memory and learning impairments in a rat model of LPS-induced neurotoxicity by modulating the ERK/SorLA/BDNF/TrkB pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Agomelatine prevented depression in the chronic restraint stress model through enhanced catalase activity and halted oxidative stress.PloS one · 2024Article
- Agomelatine enhances the therapeutic effect of venlafaxine on depression and improves the levels of S100B and GFAP.American journal of translational research · 2023Article
- Antidepressant pharmacological mechanisms: focusing on the regulation of autophagy.Frontiers in pharmacology · 2023Review
- GPNMB Modulates Autophagy to Enhance Functional Recovery After Spinal Cord Injury in Rats.Cell transplantationArticle
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundAgomelatine has been shown to be effective in the treatment of depression, but the molecular mechanisms underlying its antidepressant effects have yet to be elucidated. Identification of these molecular mechanisms would not only offer new insights into the basis for depression but also provide the foundation for the development of novel treatments for this disorder.
methodsIntraperitoneal injection of LPS was used to induce depression-like behaviors in rats. The interactions of the 5-HT2C reporter and Gαi-2 were verified by immunoprecipitation or immunofluorescence assay. Inflammatory related proteins, autophagy related proteins and apoptosis markers were verified by immunoblotting or immunofluorescence assay. Finally, electron microscopy analysis was used to observe the synapse and ultrastructural pathology.
resultsHere, we found that the capacity for agomelatine to ameliorate depression and anxiety in a lipopolysaccharide (LPS)-induced rat model of depression was associated with an alleviation of neuroinflammation, abnormal autophagy and neuronal apoptosis as well as the promotion of neurogenesis in the hippocampal dentate gyrus (DG) region of these rats. We also found that the 5-HT2C receptor is coupled with G alphai (2) (Gαi-2) protein within hippocampal neurons and, agomelatine, acting as a 5-HT2C receptor antagonist, can up-regulate activity of the Gαi-2-cAMP-PKA pathway. Such events then suppress activation of the apoptosis signal-regulating kinase 1 (ASK1) pathway, a member of the mitogen-activated protein kinase (MAPK) family involved in pathological processes of many diseases.
conclusionTaken together, these results suggest that agomelatine plays a neuroprotective role in regulating neuroinflammation, autophagy disorder and apoptosis in this LPS-induced rat model of depression, effects which are associated with the display of antidepressant behaviors. These findings provide evidence for some of the potential mechanisms for the antidepressant effects of agomelatine.
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