ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2009
Awake intranasal insulin delivery modifies protein complexes and alters memory, anxiety, and olfactory behaviors.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers.
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Who cites it
127 citing papers in PubMed, 238 citations in OpenAlex.
- Sex-Specific Neurogenic and Cognitive Responses in a Murine Model of Accelerated Aging.Aging cell · 2026Article
- The Efficacy of Intranasal Insulin in the Treatment of Post-Viral Persistent Olfactory Dysfunction: A Systematic Review.Clinical and experimental otorhinolaryngology · 2026Review
- Early-Onset Dementia Risk Escalates with Diabetes Duration: Insights from a Nationwide Cohort Study.Endocrinology and metabolism (Seoul, Korea) · 2026Article
- Intranasal insulin ameliorates prenatal LPS-induced learning and memory impairments in adolescent male rats: A behavioral, electrophysiological, and molecular study.Scientific reports · 2026Article
- The superficial tufted and mitral cell output neurons of the mouse olfactory bulb have dual roles in insulin sensing.Journal of cell science · 2025Article
- The Association Between Depression and Antidiabetic Treatments in Type 2 Diabetes Patients with Both Good and Poor Glycemic Control.Journal of clinical medicine · 2025Article
- Maternal ingestion of cannabidiol (CBD) in mice leads to sex-dependent changes in memory, anxiety, and metabolism in the adult offspring, and causes a decrease in survival to weaning age.Pharmacology, biochemistry, and behavior · 2025Article
- The subventricular zone neurogenic niche provides adult born functional neurons to repair cortical brain injuries in response to diterpenoid therapy.Stem cell research & therapy · 2025Article
- Effects of Kv1.3 knockout on pyramidal neuron excitability and synaptic plasticity in piriform cortex of mice.Acta pharmacologica Sinica · 2024Article
- Biliverdin Reductase-A integrates insulin signaling with mitochondrial metabolism through phosphorylation of GSK3β.Redox biology · 2024Article
- The effect of intra-nasal co-treatment with insulin and growth factor-rich serum on behavioral defects, hippocampal oxidative-nitrosative stress, and histological changes induced by icv-STZ in a rat model.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Insulin modulates emotional behavior through a serotonin-dependent mechanism.Molecular psychiatry · 2024Article
- Intranasal insulin attenuates hypoxia-ischemia-induced short-term sensorimotor behavioral disturbances, neuronal apoptosis, and brain damage in neonatal rats.Current research in neurobiology · 2024Article
- Targeting epidermal growth factor receptor to recruit newly generated neuroblasts in cortical brain injuries.Journal of translational medicine · 2023Article
- AAV5-mediated manipulation of insulin expression in choroid plexus has long-term metabolic and behavioral consequences.Cell reports · 2023Article
- Cardiometabolic health, menopausal estrogen therapy and the brain: How effects of estrogens diverge in healthy and unhealthy preclinical models of aging.Frontiers in neuroendocrinology · 2023Review
- Rescue of neurogenesis and age-associated cognitive decline in SAMP8 mouse: Role of transforming growth factor-alpha.Aging cell · 2023Article
- The Phosphorylation of Kv1.3: A Modulatory Mechanism for a Multifunctional Ion Channel.Cancers · 2023Review
- Brain Targeting by Intranasal Drug Delivery: Effect of Different Formulations of the Biflavone "Cupressuflavone" fromMolecules (Basel, Switzerland) · 2023Article
- Brain Targeting of Quetiapine Fumarate via Intranasal Delivery of Loaded Lipospheres: Fabrication, In-Vitro Evaluation, Optimization, and In-Vivo Assessment.Pharmaceuticals (Basel, Switzerland) · 2022Article
67 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The role of insulin pathways in olfaction is of significant interest with the widespread pathology of diabetes mellitus and its associated metabolic and neuronal comorbidities. The insulin receptor (IR) kinase is expressed at high levels in the olfactory bulb, in which it suppresses a dominant Shaker ion channel (Kv1.3) via tyrosine phosphorylation of critical N- and C-terminal residues. We optimized a 7 d intranasal insulin delivery (IND) in awake mice to ascertain the biochemical and behavioral effects of insulin to this brain region, given that nasal sprays for insulin have been marketed notwithstanding our knowledge of the role of Kv1.3 in olfaction, metabolism, and axon targeting. IND evoked robust phosphorylation of Kv1.3, as well as increased channel protein-protein interactions with IR and postsynaptic density 95. IND-treated mice had an increased short- and long-term object memory recognition, increased anxiolytic behavior, and an increased odor discrimination using an odor habituation protocol but only moderate change in odor threshold using a two-choice paradigm. Unlike Kv1.3 gene-targeted deletion that alters metabolism, adiposity, and axonal targeting to defined olfactory glomeruli, suppression of Kv1.3 via IND had no effect on body weight nor the size and number of M72 glomeruli or the route of its sensory axon projections. There was no evidence of altered expression of sensory neurons in the epithelium. In mice made prediabetic via diet-induced obesity, IND was no longer effective in increasing long-term object memory recognition nor increasing anxiolytic behavior, suggesting state dependency or a degree of insulin resistance related to these behaviors.
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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.