ArticlePloS one2012
Brain deletion of insulin receptor substrate 2 disrupts hippocampal synaptic plasticity and metaplasticity.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 2 of them syntheses that pooled it.
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Who cites it
42 citing papers in PubMed, 2 syntheses or guidelines pooled it, 72 citations in OpenAlex.
- Insulin effects on core neurotransmitter pathways involved in schizophrenia neurobiology: a meta-analysis of preclinical studies. Implications for the treatment.Molecular psychiatry · 2023Pooled it
- Relationship between Insulin Levels and Nonpsychotic Dementia: A Systematic Review and Meta-Analysis.Neural plasticity · 2017Pooled it
- Downregulation of insulin receptor isoform A in the forebrain of fetal growth-restricted rats.Pediatric research · 2026Article
- Progranulin deficiency in the brain activates an insulin signaling pathway that may promote neurodegeneration.iScience · 2026Article
- Acute Effect of Intranasal Insulin on Food Intake Among Middle-Aged African American Adults: The FIINAAL Study.Journal of the Endocrine Society · 2025Article
- Inhibition of Rho-kinase by fasudil contributes to the modulation of the synaptic plasticity response in the rat hippocampus.Pflugers Archiv : European journal of physiology · 2025Article
- Hippocampal-Specific Insulin Resistance Elicits Synaptic Effects on Glutamate Neurotransmission.Journal of neurochemistry · 2025Article
- Brain insulin signaling and cognition: Possible links.EXCLI journal · 2023Review
- ABA Supplementation Rescues IRS2 and BDNF mRNA Levels in a Triple-Transgenic Mice Model of Alzheimer's Disease.Journal of Alzheimer's disease reports · 2023Article
- Alterations in hippocampal neurogenesis and hippocampal insulin signaling pathway in rat with metabolic syndrome.Iranian journal of basic medical sciences · 2022Article
- From population to neuron: exploring common mediators for metabolic problems and mental illnesses.Molecular psychiatry · 2021Article
- Irs2 deficiency alters hippocampus-associated behaviors during young adulthood.Biochemical and biophysical research communications · 2021Article
- Molecular elevation of insulin receptor signaling improves memory recall in aged Fischer 344 rats.Aging cell · 2020Article
- Disruption of insulin receptor substrate-2 impairs growth but not insulin function in rats.The Journal of biological chemistry · 2020Article
- An update on potential links between type 2 diabetes mellitus and Alzheimer's disease.Molecular biology reports · 2020Review
- Potential role of insulin on the pathogenesis of depression.Cell proliferation · 2020Review
- Bioenergetic adaptations to HIV infection. Could modulation of energy substrate utilization improve brain health in people living with HIV-1?Experimental neurology · 2020Review
- Article
- Region-specific association between basal blood insulin and cerebral glucose metabolism in older adults.NeuroImage. Clinical · 2019Article
- High-fructose corn syrup consumption in adolescent rats causes bipolar-like behavioural phenotype with hyperexcitability in hippocampal CA3-CA1 synapses.British journal of pharmacology · 2018Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveDiabetes mellitus is associated with cognitive deficits and an increased risk of dementia, particularly in the elderly. These deficits and the corresponding neurophysiological structural and functional alterations are linked to both metabolic and vascular changes, related to chronic hyperglycaemia, but probably also defects in insulin action in the brain. To elucidate the specific role of brain insulin signalling in neuronal functions that are relevant for cognitive processes we have investigated the behaviour of neurons and synaptic plasticity in the hippocampus of mice lacking the insulin receptor substrate protein 2 (IRS-2). RESEARCH DESIGN AND
methodsTo study neuronal function and synaptic plasticity in the absence of confounding factors such as hyperglycaemia, we used a mouse model with a central nervous system- (CNS)-restricted deletion of IRS-2 (NesCreIrs2KO).
resultsWe report a deficit in NMDA receptor-dependent synaptic plasticity in the hippocampus of NesCreIrs2KO mice, with a concomitant loss of metaplasticity, the modulation of synaptic plasticity by the previous activity of a synapse. These plasticity changes are associated with reduced basal phosphorylation of the NMDA receptor subunit NR1 and of downstream targets of the PI3K pathway, the protein kinases Akt and GSK-3β.
conclusionsThese findings reveal molecular and cellular mechanisms that might underlie cognitive deficits linked to specific defects of neuronal insulin signalling.
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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 OpenQuestion graph.