ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
IκB kinase/nuclear factor κB-dependent insulin-like growth factor 2 (Igf2) expression regulates synapse formation and spine maturation via Igf2 receptor signaling.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 2 of them syntheses that pooled it.
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Who cites it
85 citing papers in PubMed, 2 syntheses or guidelines pooled it, 138 citations in OpenAlex.
- Neurobiological mechanisms of olfactory dysfunction: a ten-year bibliometric and visualization analysis.Frontiers in medicine · 2026Pooled it
- Adult brain neurons require continual expression of the schizophrenia-risk gene Tcf4 for structural and functional integrity.Translational psychiatry · 2021Pooled it
- Distribution and Levels of Insulin-like Growth Factor 2 Receptor Across Mouse Brain Cell Types.Receptors (Basel, Switzerland) · 2026Article
- Molecular mechanism of Alzheimer's disease using integrated multi-omics.Frontiers in aging neuroscience · 2026Review
- A prodrug targeting CIM6P/IGF2R enhances memory in healthy mice and reverses deficits in an Angelman syndrome mouse model.Translational psychiatry · 2025Article
- Insulin-Like Growth Factor 2 Reverses Synaptic and Cognitive Deficits in Fetal Growth Restriction Mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Insulin-Like Growth Factor Signaling in Alzheimer's Disease: Pathophysiology and Therapeutic Strategies.Molecular neurobiology · 2025Review
- Role of CYLD in brain physiology and pathology.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Neuroprotective effects of baicalin and baicalein on the central nervous system and the underlying mechanisms.Heliyon · 2025Review
- Skeletal stem/progenitor cell-derived rather than osteoblast-derived IGF2 supports the development and homeostasis of skeletal system via STAT3.International journal of biological sciences · 2025Article
- Fire Acupuncture Combined with Pulse Radiofrequency Relieves Tactile Allodynia in Rats with Postherpetic Neuralgia.International journal of general medicine · 2025Article
- Premature cognitive decline in a mouse model of tuberous sclerosis.Aging cell · 2024Article
- Diversity of Microglia-Derived Molecules with Neurotrophic Properties That Support Neurons in the Central Nervous System and Other Tissues.Molecules (Basel, Switzerland) · 2024Review
- NF-κB in Alzheimer's Disease: Friend or Foe? Opposite Functions in Neurons and Glial Cells.International journal of molecular sciences · 2024Review
- A Map of Transcriptomic Signatures of Different Brain Areas in Alzheimer's Disease.International journal of molecular sciences · 2024Article
- Targeting IGF2 to reprogram the tumor microenvironment for enhanced viro-immunotherapy.Neuro-oncology · 2024Article
- Integrative Metabolomics and Whole Transcriptome Sequencing Reveal Role for TREM2 in Metabolism Homeostasis in Alzheimer's Disease.Molecular neurobiology · 2024Article
- Oxidative Effects in Early Stages of Embryo Development Due to Alcohol Consumption.International journal of molecular sciences · 2024Review
- Role of insulin-like growth factor-2 in Alzheimer's disease induced memory impairment and underlying mechanisms.Frontiers in cellular neuroscience · 2024Review
- Article
25 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alterations of learning and memory in mice with deregulated neuron-specific nuclear factor κB (NF-κB) activity support the idea that plastic changes of synaptic contacts may depend at least in part on IκB kinase (IKK)/NF-κB-related synapse-to-nucleus signaling. There is, however, little information on the molecular requirements and mechanisms regulating this IKK/NF-κB-dependent synapse development and remodeling. Here, we report that the NF-κB inducing IKK kinase complex is localized at the postsynaptic density (PSD) and activated under basal conditions in the adult mouse brain. Using different models of conditional genetic inactivation of IKK2 function in mouse principal neurons, we show that IKK/NF-κB signaling is critically involved in synapse formation and spine maturation in the adult brain. IKK/NF-κB blockade in the forebrain of mutant animals is associated with reduced levels of mature spines and postsynaptic proteins PSD95, SAP97, GluA1, AMPAR-mediated basal synaptic transmission and a spatial learning impairment. Synaptic deficits can be restored in adult animals within 1 week by IKK/NF-κB reactivation, indicating a highly dynamic IKK/NF-κB-dependent regulation process. We further identified the insulin-like growth factor 2 gene (Igf2) as a novel IKK/NF-κB target. Exogenous Igf2 was able to restore synapse density and promoted spine maturation in IKK/NF-κB signaling-deficient neurons within 24 h. This process depends on Igf2/Igf2R-mediated MEK/ERK activation. Our findings illustrate a fundamental role of IKK/NF-κB-Igf2-Igf2R signaling in synapse formation and maturation in adult mice, thus providing an intriguing link between the molecular actions of IKK/NF-κB in neurons and the memory enhancement factor Igf2.
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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.