ArticleFrontiers in physiology2020
Neuroprotective Effects of Fluoxetine Against Chronic Stress-Induced Neural Inflammation and Apoptosis: Involvement of the p38 Activity.
Article in Frontiers in physiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Emerging Therapeutic Potential of Fluoxetine on Cognitive Decline in Alzheimer's Disease: Systematic Review.International journal of molecular sciences · 2024Pooled it
- Exercise and fluoxetine in Alzheimer's disease: Molecular mechanisms of synergistic and antagonistic effects (Review).International journal of molecular medicine · 2026Review
- Development and characterization of a reserpine-induced mouse model of depression: An integrated in-vivo and in-silico approach.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Deacetyl xylopic acid exhibits synergistic antidepressant-like effects and augments fluoxetine activity in a chronic restraint-induced depression model in mice.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- GV-971 Ameliorates Chronic Restraint Stress-Induced Depression-like Phenotypes Accompanied by Reshaping of the Microbiota-Gut-Brain Axis.Marine drugs · 2026Article
- Akkermansia Muciniphila vs. Fluoxetine: Amelioration of Depression-like Behaviors and Cognitive Dysfunction Through Distinct Neurobiological Mechanisms.Probiotics and antimicrobial proteins · 2026Article
- Advancing Antidepressive Agents: Drug Discovery and Polymer-Based Drug Delivery Systems for Improved Treatment Outcome.Biomedicines · 2025Review
- Article
- Study on the Neuroprotective Effects of Eight Iridoid Components Using Cell Metabolomics.Molecules (Basel, Switzerland) · 2024Article
- Elevated Expression of HSP72 in the Prefrontal Cortex and Hippocampus of Rats Subjected to Chronic Mild Stress and Treated with Imipramine.International journal of molecular sciences · 2023Article
- Fluoxetine Protects Retinal Ischemic Damage in Mice.Pharmaceutics · 2023Article
- Aortic ischemia-reperfusion injury and potency of fluoxetine.Iranian journal of basic medical sciences · 2023Article
- Article
- The role of the immune system in posttraumatic stress disorder.Translational psychiatry · 2022Review
- Article
- Necroptotic kinases are involved in the reduction of depression-induced astrocytes and fluoxetine's inhibitory effects on necroptotic kinases.Frontiers in pharmacology · 2022Article
- Chinese Herbal Medicine for the Treatment of Depression: Effects on the Neuroendocrine-Immune Network.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Xiaoyaosan Alleviates Hippocampal Glutamate-Induced Toxicity in the CUMS Rats via NR2B and PI3K/Akt Signaling Pathway.Frontiers in pharmacology · 2021Article
- Carvacrol attenuated neuroinflammation, oxidative stress and depression and anxiety like behaviors in lipopolysaccharide-challenged rats.Avicenna journal of phytomedicineArticle
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Depression is considered a widespread neuropsychiatric disease associated with neuronal injury within specific brain regions. Fluoxetine, a selective serotonin reuptake inhibitor, has been widely used in depressed patients. Recently, fluoxetine has demonstrated neuroprotective effects apart from the effect on serotonin. However, the underlying mechanism involved in this neuroprotection remains unclear, in particular, whether fluoxetine exerts antidepressant effects via protecting against neuronal injury. Here, we found that treatment with fluoxetine (10 mg/kg, i.p.) for 2 weeks ameliorated depression-like behaviors in a chronic unpredictable mild stress (CUMS)-induced rat model of depression and was accompanied with an alleviation of glia activation and inhibition of interleukin-1β (IL-1β), interferon gamma (IFN-γ), and tumor necrosis factor-α (TNF-α) expression in the hippocampal dentate gyrus (DG) region. Meanwhile, CUMS rats treated with fluoxetine showed reductions in neuronal apoptosis and a downregulation of the apoptotic protein Bax, cleaved caspase 3, and caspase 9 levels. These effects appear to involve a downregulation of p38 mitogen-activated protein kinase (MAPK) signaling within the DG hippocampus as the specific inhibitor of p38 MAPK, SB203580, significantly suppressed apoptosis, as well as ameliorated depressive behaviors resulting from CUMS exposure. Moreover, fluoxetine could rescue neuronal deterioration and depression-like phenotypes caused by overexpression of p38 in DG. This finding extends our knowledge on the antidepressant-like effects of fluoxetine, which appear to at least partially profit from neuroprotection against inflammation and neuronal apoptosis via downregulation of the p38 MAPK pathway. The neuroprotective mechanisms of fluoxetine may provide some novel therapeutic avenues for stress-related neurological diseases.
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