ArticleMolecular neurobiology2024
Levomilnacipran Improves Lipopolysaccharide-Induced Dysregulation of Synaptic Plasticity and Depression-Like Behaviors via Activating BDNF/TrkB Mediated PI3K/Akt/mTOR Signaling Pathway.
Article in Molecular neurobiology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Natural antidepressants in neuroimmunomodulation: molecular mechanisms, action targets, and therapeutic potential.Frontiers in immunology · 2025Pooled it
- PI3K-Akt signaling network crosstalk in cerebral ischemia/reperfusion injury: Mechanisms and therapeutic implications.Chinese medical journal · 2026Review
- Gut Microbiota and Metabolites: Orchestrating Depression Pathogenesis Through the Microbiota-Gut-Brain Axis's Neural, Immune, and Metabolic Routes.Biomolecules · 2026Review
- Postbiotic Lactobacillus reuteri LRE02 Enriched with Sodium Selenite Demonstrates Antidepressant- and Anxiolytic-Like Effects in Mice.Molecular neurobiology · 2026Article
- Ginsenoside Rh2 Protects Against Glutamate-Induced Neurotoxicity in PC12 Cells via Activation of the VEGF-mediated PI3K/Akt/mTOR Signaling Pathway.Neurochemical research · 2026Article
- Mitochondrial dysfunction in neonatal brain injury: from molecular mechanisms to therapeutic interventions.Journal of translational medicine · 2026Review
- Redefining Parkinson's Disease management: the synergistic role of neurotrophic factors and mitochondria.Cellular and molecular life sciences : CMLS · 2026Review
- Molecular mechanisms underlying cyclophosphamide-induced ovarian injury and protective strategies.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Exercise as a multiscale recalibration of stress-related homeostatic balance.Frontiers in neuroscience · 2026Review
- Lidocaine for Depressive Symptoms and Comorbid Pain: A Narrative Review of Mechanisms, Evidence, and Safety.Drug design, development and therapy · 2026Review
- Alterations in Neuroinflammation, Microglia and Neuroplasticity in the Rat Hippocampus in a Combined Model of Periodontitis and Depression.CNS neuroscience & therapeutics · 2025Article
- Prenatal depression-associated gut microbiota induces depressive-like behaviors and hippocampal neuroinflammation in germ-free mice.Translational psychiatry · 2025Article
- ZDHHC5 Mediates Immune Dysregulation Driving Generalized Anxiety Disorder Risk.Brain and behavior · 2025Article
- CD9, a novel potential biomarker of sarcopenia.Scientific reports · 2025Article
- Advancing Antidepressive Agents: Drug Discovery and Polymer-Based Drug Delivery Systems for Improved Treatment Outcome.Biomedicines · 2025Review
- Human Umbilical Cord Mesenchymal Stem Cells Ameliorated Chronic Unpredictable Mild Stress-Induced Depression and Anxiety by Alleviating Neuroinflammation.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- The TAAR1 Agonist PCC0105004 Regulates Amygdala Synaptic Plasticity to Alleviate Anxiety-Like Behaviors in Rats.Pharmacology research & perspectives · 2025Article
- Astrocytic pleiotrophin deficiency in the prefrontal cortex contributes to stress-induced depressive-like responses in male mice.Nature communications · 2025Article
- Vascular endothelial growth factor: a key factor in the onset and treatment of depression.Frontiers in cellular neuroscience · 2025Review
- Corticosterone-induced postpartum depression induces depression-like behavior and impairs hippocampal neurogenesis in adolescent offspring via HPA axis and BDNF-mTOR pathway.Neurobiology of stress · 2025Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Depression is a common psychological disease with high morbidity and mortality. Recently, the involvement of synaptic plasticity in the pathogenesis of depression has shed light on the direction of developing novel antidepressants. Levomilnacipran is a newly approved medication for the treatment of adult major depressive disorder. However, the detailed mechanisms underlying its antidepressant-like effects have yet to be illuminated. In this study, we aimed to investigate the role of levomilnacipran in regulating synaptic plasticity and explore the possible molecular mechanisms of its antidepressant effects using a rat model of depression induced by lipopolysaccharide (LPS). The results demonstrated that levomilnacipran (30 mg/kg, i.p.) significantly ameliorated depression-like behaviors in rats, alleviated the dysregulation of synaptic plasticity, and suppressed neuroinflammation within hippocampus induced by LPS-treatment. Levomilnacipran increased the expression of postsynaptic dense 95 (PSD-95) and synaptophysin (Syn) and reversed the imbalance between pro- and anti-inflammatory cytokines within hippocampus of depressed rats. Additionally, levomilnacipran elevated expression level of brain-derived neurotrophic factor (BDNF), accompanied by increased tyrosine kinase B (TrkB), phosphorylated phosphatidylinositol 3-kinase (PI3K), phosphorylated protein kinase B (p-Akt), and phosphorylated mammalian target of rapamycin (p-mTOR). Taken together, these results suggest that levomilnacipran may exert antidepressant effects via upregulating BDNF/TrkB mediated PI3K/Akt/mTOR signaling pathway to improve synaptic plasticity. These findings reveal potential mechanisms for the antidepressant effects of levomilnacipran and offer new insights into the treatments for depression.
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Registered trials
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.