ArticleJournal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology2025
Exploring Dapagliflozin's Influence on Autophagic Flux in Mania-like Behaviour: Insights from the LKB1/AMPK/LC3 Pathway in a Mouse Model.
Article in Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed.
- The role of immune cell phenotypes and metabolites in bipolar disorder risk: a Mendelian randomization-based mediation analysis.European archives of psychiatry and clinical neuroscience · 2026Article
- Sodium-Glucose Cotransporter-2 Inhibitors in Mood Disorders: A Narrative Review of Mechanisms, Evidence, and Challenges.Neuropsychiatric disease and treatment · 2026Review
- TLR-4/Notch1/NF-κB pathway modulation by dapagliflozin: a novel mechanism for neuroprotection in hepatic encephalopathy.Metabolic brain disease · 2025Article
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4 authors.
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Abstract
Mania-like episodes are neuropsychiatric disturbances associated with bipolar disorder (BD). Autophagic flux disturbance evolved as one of the molecular mechanisms implicated in mania. Recently, Dapagliflozin (DAPA) has corrected autophagic signaling in several neurological disorders. Yet, no endeavours examined the autophagic impact of DAPA in mania-like behaviours. This study aimed to investigate the effect of DAPA on disrupted autophagic pathways in a mouse model of mania-like behaviour. Mania-like behaviour was induced through paradoxical sleep deprivation (PSD) using the multiple-platform method for a duration of 36 h. Mice were divided into three groups, with DAPA (1 mg/kg/day, orally) administered for one week. Behavioural assessments were conducted on the 7th day. DAPA mitigated anxiety-like behaviour in the open field test and improved motor coordination and muscle tone in the rotarod test. Mechanistically, DAPA activated hippocampal autophagy-related markers; liver kinase B1/AMP-activated protein kinase (LKB1/AMPK) pathway, autophagy related gene 7 (ATG7), and microtubule-associated protein light chain 3II (LC3II). This was associated with reduced levels of the autophagosome receptor p62 protein, which subsequently enhanced GABA
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