ArticleJournal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology2023
PCSK9 Inhibition Reduces Depressive like Behavior in CUMS-Exposed Rats: Highlights on HMGB1/RAGE/TLR4 Pathway, NLRP3 Inflammasome Complex and IDO-1.
Article in Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 31 citations in OpenAlex.
- Cardioprotective role of vincamine in cyclophosphamide-induced cardiotoxicity through modulation of AMPK/SIRT1, PI3K/Akt, and MAPK pathways.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- PACSIN2-mediated synaptic injury contributes to behavioral disorders caused by chronic stress.Acta pharmacologica Sinica · 2026Article
- Chronic unpredictable mild Stress- induced neurobehavioral and metabolic alteration: insights into molecular mechanisms and emerging therapeutic Strategies".Psychopharmacology · 2026Review
- The role of metabolic disorders in major depressive disorder.Molecular biology reports · 2026Review
- Reduced Serum Soluble L-Selectin Levels but Not PCSK9 May Be Associated With Generalized Anxiety Disorder: A Case-Control Study.Journal of clinical laboratory analysis · 2026Article
- Mechanisms of action and therapeutic potential of PCSK9-regulating drugs.Pharmaceutical biology · 2025Review
- Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) in Alzheimer's Disease: Recent Advances and Controversies.Molecular neurobiology · 2025Review
- Lactobacillus fermentum ATCC 9338 ameliorates immune dysregulation via indoleamine 2, 3-dioxygenase through modulating gut microbial diversity of chronic unpredictable mild stressed mouse.Metabolic brain disease · 2025Article
- Do immune system and microbiome-gut-brain axis interactions associate with major depressive disorder?Journal of translational medicine · 2025Review
- Mitigating atherosclerosis: Integrating vaccines with gene targets.American heart journal plus : cardiology research and practice · 2025Review
- Association of HMGB1, IL-1β, IL-8, IL-10, and MCP-1 with the Development of Systemic Inflammatory Response Syndrome in Pediatric Patients with Recently Diagnosed Acute Lymphoblastic Leukemia.Life (Basel, Switzerland) · 2025Article
- Role of Probiotics in Depression: Connecting Dots of Gut-Brain-Axis Through Hypothalamic-Pituitary Adrenal Axis and Tryptophan/Kynurenic Pathway involving Indoleamine-2,3-dioxygenase.Molecular neurobiology · 2025Review
- NLRP3 Inflammasome: A New Target for the Treatment of CVD and Depression Comorbidity.Mediators of inflammation · 2025Review
- Corticosterone effects induced by stress and immunity and inflammation: mechanisms of communication.Frontiers in endocrinology · 2025Review
- Involvement of role of HMGB1-NLRP3 pathway in systemic disorders.Frontiers in cell and developmental biology · 2025Review
- The Emerging Role of PCSK9 in the Pathogenesis of Alzheimer's Disease: A Possible Target for the Disease Treatment.International journal of molecular sciences · 2024Review
- Depression, stress, and tryptophan metabolism through the kynurenine pathway: treatment strategies from the perspective of Chinese herbal medicine.Metabolic brain disease · 2024Review
- Unraveling the rapid progression of non-target lesions: risk factors and the therapeutic potential of PCSK9 inhibitors in post-PCI patients.BMC cardiovascular disorders · 2024Article
- Inflammatory markers, oxidative stress, and mitochondrial dynamics: Repercussions on coronary artery disease in diabetes.World journal of diabetes · 2024Article
- Chronic Stress-Induced Neuroinflammation: Relevance of Rodent Models to Human Disease.International journal of molecular sciences · 2024Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ample evidence has pointed to a close link between cardiovascular diseases (CVD) and depression. Inflammatory pathways including the high-mobility-group-box-1 protein, receptor-for-advanced-glycation-end-products and toll-like-receptor-4 (HMGB1/RAGE/TLR4) and nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome pathways are thought to be crucial players in this link. Activation of these pathways ends by releasing of different inflammatory mediators involved in CVD and depression pathophysiology. In the brain, this inflammatory process enhanced indoleamine2,3-dioxygenase-1 (IDO-1) activation with subsequent alteration in kynurenine/tryptophan levels causing depression. Based on the favorable anti-inflammatory effects of Alirocumab, the proprotein-convertase-subtilisin/kexin-type-9 (PCSK9) inhibitor, used in different CVD, this study was designed to investigate its potential antidepressant effect. The behavioral and neurochemical effects of concomitant treatment of Alirocumab at doses of (4, 8 and 16 mg/kg/week subcutaneously) in Wistar rats exposed to chronic unpredictable mild stress (CUMS) for 6 weeks were assayed. Alirocumab prevented CUMS-induced depressive-like-behaviors exhibited in open-field and forced-swimming tests, and hypothalamus-pituitary-adrenal axis hyperactivity (adrenal gland weight and serum corticosterone). Alirocumab prevented CUMS-induced alteration in hippocampal kynurenine/tryptophan levels and pro-inflammatory cytokines tumor-necrosis-factor-alpha, interleukin-1beta (IL-1β), IL-2 and IL-6. Western blot and PCR analysis showed that Alirocumab favorably modulated the HMGB1/RAGE/TLR4 axis, nuclear-factor-kappa-beta, NLRP3 inflammasome complex and IDO-1 in the hippocampus of CUMS rats. These effects were correlated to the level of PCSK9 expression. The behavioral and biochemical findings indicated the potential antidepressant effect of PCSK9 inhibition by Alirocumab.
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