ArticleFrontiers in aging neuroscience2021
Amelioration of Hippocampal Insulin Resistance Reduces Tau Hyperphosphorylation and Cognitive Decline Induced by Isoflurane in Mice.
Article in Frontiers in aging neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Effect of antidiabetic drugs in Alzheimer´s disease: a systematic review of preclinical and clinical studies.Molecular neurodegeneration · 2025Pooled it
- Peripheral metabolic dysfunction is associated with cognitive frailty in a mouse model of type 2 diabetes.Metabolic brain disease · 2026Article
- Inhaled General Anesthetics in Alzheimer's Disease Progression: Divergent Effects, Underlying Mechanisms, and Future Perspectives.Molecular neurobiology · 2026Review
- Article
- Isoflurane and Surgical Stress Disrupt Fatty Acid and Carbon Metabolism Leading to Cardiomyopathy.bioRxiv : the preprint server for biology · 2025Article
- Advances in research on the pathogenesis and signaling pathways associated with postoperative delirium (Review).Molecular medicine reports · 2025Review
- What Information do Systemic Pathological Changes Bring to the Diagnosis and Treatment of Alzheimer's Disease?Neuroscience bulletin · 2025Review
- Dapagliflozin Improves High-Fat Diet-Induced Cognitive Impairment in Female Mice.Brain and behavior · 2025Article
- Beneficial Effects of Echinacoside on Cognitive Impairment and Diabetes in Type 2 Diabetic db/db Mice.Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association · 2024Article
- Moderate aerobic training enhances the effectiveness of insulin therapy through hypothalamic IGF1 signaling in rat model of Alzheimer's disease.Scientific reports · 2024Article
- Metformin: The Winding Path from Understanding Its Molecular Mechanisms to Proving Therapeutic Benefits in Neurodegenerative Disorders.Pharmaceuticals (Basel, Switzerland) · 2023Review
- PPARα agonist fenofibrate prevents postoperative cognitive dysfunction by enhancing fatty acid oxidation in mice.Translational neuroscience · 2023Article
- Decoding the genetic relationship between Alzheimer's disease and type 2 diabetes: potential risk variants and future direction for North Africa.Frontiers in aging neuroscience · 2023Article
- Enhancement of astrocytic gap junctions Connexin43 coupling can improve long-term isoflurane anesthesia-mediated brain network abnormalities and cognitive impairment.CNS neuroscience & therapeutics · 2022Article
- The Role of Insulin Signaling in Hippocampal-Related Diseases: A Focus on Alzheimer's Disease.International journal of molecular sciences · 2022Review
- Metformin alleviates prolonged isoflurane inhalation induced cognitive decline via reducing neuroinflammation in adult mice.International immunopharmacology · 2022Article
- Connexin 43 gap junction-mediated astrocytic network reconstruction attenuates isoflurane-induced cognitive dysfunction in mice.Journal of neuroinflammation · 2022Article
- Alpha-Ketoglutarate Alleviates Neuronal Apoptosis Induced by Central Insulin Resistance through Inhibiting S6K1 Phosphorylation after Subarachnoid Hemorrhage.Oxidative medicine and cellular longevity · 2022Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
General anesthetics can induce cognitive impairments and increase the risk of Alzheimer's disease (AD). However, the underlying mechanisms are still unknown. Our previous studies shown that long-term isoflurane exposure induced peripheral and central insulin resistance (IR) in adult mice and aggravated IR in type 2 diabetes mellitus (T2DM) mice. Clinical and preclinical studies revealed an association between impaired insulin signaling and tau pathology in AD and other tauopathies. We investigated if alleviation of hippocampal IR by the antidiabetic agent metformin could reduce tau hyperphosphorylation and cognitive decline induced by isoflurane in mice. The effects of prolonged (6 h) isoflurane anesthesia on hippocampal IR, hippocampal tau hyperphosphorylation, and hippocampus-dependent cognitive function were evaluated in wild type (WT) adult mice and the high-fat diet plus streptozotocin (HFD/STZ) mouse model of T2DM. Here we shown that isoflurane and HFD/STZ dramatically and synergistically induced hippocampal IR and fear memory impairment. Metformin pretreatment strongly ameliorated hippocampal IR and cognitive dysfunction caused by isoflurane in WT mice, but was less effective in T2DM mice. Isoflurane also induced hippocampal tau hyperphosphorylation and metformin reversed this effect. In addition, isoflurane significantly increased blood glucose levels in both adult and T2DM mice, and metformin reversed this effect as well. Administration of 25% glucose to metformin-pretreated mice induced hyperglycemia, but surprisingly did not reverse the benefits of metformin on hippocampal insulin signaling and fear memory following isoflurane anesthesia. Our findings show hippocampal IR and tau hyperphosphorylation contribute to acute isoflurane-induced cognitive dysfunction. Brief metformin treatment can mitigate these effects through a mechanism independent of glycemic control. Future studies are needed to investigate whether long-term metformin treatment can also prevent T2DM-induced hippocampal IR and cognitive decline.
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Registered trials
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 Socratic graph.