ArticleBrain and behavior2025
Dapagliflozin Improves High-Fat Diet-Induced Cognitive Impairment in Female Mice.
Article in Brain and behavior, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
5 citing papers in PubMed.
- Glucose-Lowering Therapies and Cognitive Decline: From Molecular Mechanisms to Clinical Evidence and Future Perspectives.Advances in therapy · 2026Review
- The Liver-brain Axis: A Three-stage Model Linking MASLD to Cognitive Impairment and Dementia.Journal of molecular neuroscience : MN · 2026Review
- Mechanistic Links Between the Gut Microbiome and Longevity Therapeutics.Biomedicines · 2026Review
- Sodium-Glucose Cotransporter-2 Inhibitors in Mood Disorders: A Narrative Review of Mechanisms, Evidence, and Challenges.Neuropsychiatric disease and treatment · 2026Review
- Dapagliflozin Ameliorates Doxorubicin-Induced Chemobrain and Cognitive Abnormalities in Rats: Modulation of AKT/GSK-3β and Wnt/β-Catenin Pathways.Neurochemical research · 2025Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
backgroundHigh fat consumption is a known risk factor for the development of type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD). Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have been found to possess anti-inflammatory and neuroprotective properties. However, the cognitive effects and mechanisms of SGLT2is on female mice fed with a high-fat diet remain unknown.
objectiveThis study aimed to investigate the impacts of dapagliflozin on metabolism, cognition, neuroinflammation, insulin resistance, and microglial activation in female mice fed a HFD.
methodsDapagliflozin (1 mg/kg) was administered to HFD-fed mice for 24 weeks. Body weight, glucose tolerance, and insulin resistance were assessed. Additionally, all mice were subjected to the Morris water maze (MWM) and one-trial Y-maze tests. The levels of metabolic hormones and cytokines were analyzed using ELISA kits. The levels of phosphorylated tau (p-tau) protein in the hippocampus were measured. Microglia, insulin receptors, NLRP3, and IL-1β in the hippocampus of mice were evaluated by immunofluorescence or immunohistochemical staining.
resultsAs anticipated, dapagliflozin improved insulin resistance and glucose metabolism and reduced cognitive impairment in female mice fed with a HFD. In the hippocampus, dapagliflozin alleviated microglial activation yet did not reduce the secretion of inflammatory chemokines. Furthermore, it increased the expression of insulin receptor in the hippocampus of HFD-fed mice and decreased the expression of p-tau.
conclusionsOur results provide a foundation for the clinical application of SGLT2is as an adjuvant to slow down the progression of central degenerative diseases related to metabolic disorders, such as AD.
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