ArticleMolecular & cellular proteomics : MCP2018
Metabolomic Analysis Identifies Lactate as an Important Pathogenic Factor in Diabetes-associated Cognitive Decline Rats.
Article in Molecular & cellular proteomics : MCP, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 55 citations in OpenAlex.
- Estradiol Replacement Modulates Synaptic Transmission-Related Proteins in the Hippocampus of Ovariectomized Rats: An Exploratory Proteomic Approach.Journal of neurochemistry · 2026Article
- Hippocampal Mitochondrial Dysfunction and Synaptic Disruption Link Organophosphate Exposure to Pre-Diabetes: An LC-MS/MS-Based Proteomics Approach.Biomolecules · 2026Article
- Admission lactate at ICU entry and the risk of postoperative delirium after cardiac surgery: a retrospective cohort study using the eICU-CRD database.BMC cardiovascular disorders · 2026Article
- Histone lactylation modification and its role in cerebral ischemia-reperfusion injury (Review).Biomedical reports · 2026Review
- Integrative Multi-Analysis Identifies METTL3-Regulated FGF19 and H6PD as Candidate Targets in Diabetic Cognitive Impairment.Biomolecules · 2026Article
- Acceleration of Lactate Uptake and Utilization Contributes to Neuroprotective Action of FGF21 Involved in Naturally Aging Mice.Aging cell · 2026Article
- Therapeutic potential ofFrontiers in behavioral neuroscience · 2026Article
- Lactate and cognition: a dual modulator.Frontiers in molecular neuroscience · 2026Review
- H3K18 lactylation potentiates microglial polarization via the TLR4 pathway in diabetes-induced cognitive impairment.JCI insight · 2025Article
- H4K12 lactylation potentiates mitochondrial oxidative stress via the Foxo1 pathway in diabetes-induced cognitive impairment.Journal of advanced research · 2025Article
- Crosstalk between skeletal muscle and the brain during physical activity - in search of epigenetic mechanisms.Epigenetics · 2025Review
- Brain endothelial HIF-1Acta pharmaceutica Sinica. B · 2025Article
- DNA damage in proximal tubules triggers systemic metabolic dysfunction through epigenetically altered macrophages.Nature communications · 2025Article
- Mechanisms for Regulatory Effects of Exercise on Metabolic Diseases from the Lactate-Lactylation Perspective.International journal of molecular sciences · 2025Review
- High Rosmarinic Acid ContentAntioxidants (Basel, Switzerland) · 2025Article
- The Effects of Exercise on Hippocampus-Based Cognitive Dysfunction in Type 2 Diabetes Mellitus: A Possible Involvement of Hippocampal Monocarboxylate Transporter 2.Advances in neurobiology · 2025Review
- Review
- Untargeted Metabolomic Profiling Reveals Differentially Expressed Serum Metabolites and Pathways in Type 2 Diabetes Patients with and without Cognitive Decline: A Cross-Sectional Study.International journal of molecular sciences · 2024Article
- Fibroblast growth factor 21 alleviates diabetes-induced cognitive decline.Cerebral cortex (New York, N.Y. : 1991) · 2024Article
- Risk factors and metabolomics of mild cognitive impairment in type 2 diabetes mellitus.Frontiers in molecular biosciences · 2024Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diabetes mellitus causes brain structure changes and cognitive decline, and it has been estimated that diabetes doubles the risk for dementia. Until now, the pathogenic mechanism of diabetes-associated cognitive decline (DACD) has remained unclear. Using metabolomics, we show that lactate levels increased over time in the hippocampus of rats with streptozotocin-induced diabetes, as compared with age-matched control rats. Additionally, mRNA levels, protein levels, and enzymatic activity of lactate dehydrogenase-A (LDH-A) were significantly up-regulated, suggesting increased glycolysis activity. Importantly, by specifically blocking the glycolysis pathway through an LDH-A inhibitor, chronic diabetes-induced memory impairment was prevented. Analyzing the underlying mechanism, we show that the expression levels of cAMP-dependent protein kinase and of phosphorylated transcription factor cAMP response element-binding proteins were decreased in 12-week diabetic rats. We suggest that G protein-coupled receptor 81 mediates cognitive decline in the diabetic rat. In this study, we report that progressively increasing lactate levels is an important pathogenic factor in DACD, directly linking diabetes to cognitive dysfunction. LDH-A may be considered as a potential target for alleviating or treating DACD in the future.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.