ArticleMolecular metabolism2019
Cognitive dysfunction in diabetic rats is prevented by pyridoxamine treatment. A multidisciplinary investigation.
Article in Molecular metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
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- Risk Factors, Pathological Changes, and Potential Treatment of Diabetes-Associated Cognitive Dysfunction.Journal of diabetes · 2025Review
- Mechanisms underlying cognitive impairment and management strategies in type 2 diabetes.Frontiers in endocrinology · 2025Review
- Subchronic effects of HgClFrontiers in toxicology · 2025Article
- A pathophysiological intersection between metabolic biomarkers and memory: a longitudinal study in the STZ-induced diabetic mouse model.Frontiers in physiology · 2025Article
- Mitigating diabetes associated with reactive oxygen species (ROS) and protein aggregation through pharmacological interventions.RSC advances · 2024Review
- Hippocampal proteins discovery of Panax quinquefolius and Acorus gramineus ameliorating cognitive impairment in diabetic rats.Psychopharmacology · 2023Article
- Pyridoxamine treatment ameliorates large artery stiffening and cerebral artery endothelial dysfunction in old mice.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Article
- Hydrogen Sulfide Plays an Important Role by Regulating Endoplasmic Reticulum Stress in Diabetes-Related Diseases.International journal of molecular sciences · 2022Review
- Effects ofMolecules (Basel, Switzerland) · 2022Article
- Capsaicin Ameliorates the Loosening of Mitochondria-Associated Endoplasmic Reticulum Membranes and Improves Cognitive Function in Rats With Chronic Cerebral Hypoperfusion.Frontiers in cellular neuroscience · 2022Article
- Swimming training and Plantago psyllium ameliorate cognitive impairment and glucose tolerance in streptozotocin-nicotinamide-induced type 2 diabetic rats.The journal of physiological sciences : JPS · 2021Article
- Article
- Experimental long-term diabetes mellitus alters the transcriptome and biomechanical properties of the rat urinary bladder.Scientific reports · 2021Article
- SIRT1 Mediates HNeurochemical research · 2021Article
- Schisandrin ameliorates cognitive deficits, endoplasmic reticulum stress and neuroinflammation in streptozotocin (STZ)-induced Alzheimer's disease rats.Experimental animals · 2020Article
- Systemic vitamin intake impacting tissue proteomes.Nutrition & metabolism · 2020Review
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
objectiveThe impact of diabetes mellitus on the central nervous system is less widely studied than in the peripheral nervous system, but there is increasing evidence that it elevates the risk of developing cognitive deficits. The aim of this study was to characterize the impact of experimental diabetes on the proteome and metabolome of the hippocampus. We tested the hypothesis that the vitamin B6 isoform pyridoxamine is protective against functional and molecular changes in diabetes.
methodsWe tested recognition memory using the novel object recognition (NOR) test in streptozotocin (STZ)-induced diabetic, age-matched control, and pyridoxamine- or insulin-treated diabetic male Wistar rats. Comprehensive untargeted metabolomic and proteomic analyses, using gas chromatography-mass spectrometry and iTRAQ-enabled protein quantitation respectively, were utilized to characterize the molecular changes in the hippocampus in diabetes.
resultsWe demonstrated diabetes-specific, long-term (but not short-term) recognition memory impairment and that this deficit was prevented by insulin or pyridoxamine treatment. Metabolomic analysis showed diabetes-associated changes in 13/82 identified metabolites including polyol pathway intermediates glucose (9.2-fold), fructose (4.9-fold) and sorbitol (5.2-fold). We identified and quantified 4807 hippocampal proteins; 806 were significantly altered in diabetes. Pathway analysis revealed significant alterations in cytoskeletal components associated with synaptic plasticity, glutamatergic signaling, oxidative stress, DNA damage and FXR/RXR activation pathways in the diabetic rat hippocampus.
conclusionsOur data indicate a protective effect of pyridoxamine against diabetes-induced cognitive deficits, and our comprehensive 'omics datasets provide insight into the pathogenesis of cognitive dysfunction enabling development of further mechanistic and therapeutic studies.
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