ArticleNature medicine2017
Epigenetic suppression of hippocampal calbindin-D28k by ΔFosB drives seizure-related cognitive deficits.
Article in Nature medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 1 of them a synthesis that pooled it.
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Who cites it
73 citing papers in PubMed, 1 synthesis or guideline pooled it, 115 citations in OpenAlex.
- Decreased Brain pH Correlated With Progression of Alzheimer Disease Neuropathology: A Systematic Review and Meta-Analyses of Postmortem Studies.The international journal of neuropsychopharmacology · 2024Pooled it
- Voluntary Physical Activity Modulates Brain ΔFOSB and Alters Coactivation Networks in Male and Female Mice.eNeuro · 2026Article
- Targeting C/EBPβ/ Calbindin 1 pathway bolsters the neural resilience to tau pathology and improves tau-impaired episodic memory.Molecular psychiatry · 2026Article
- Repetitive neuronal activation regulates cellular maturation state via nuclear reprogramming.Nature communications · 2026Article
- Calbindin-D28k deficiency mediates tau-driven hippocampal hyperexcitement and cognitive impairment.Translational neurodegeneration · 2026Article
- Hyper-maturity and accelerated aging in the hippocampus of mouse models of neuropsychiatric disorders with anxiety-like behavior.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Efficient In Vivo Pharmacological Inhibition of ΔFOSB, an AP-1 Transcription Factor, in the Brain.ACS chemical neuroscience · 2026Article
- Multiparity exacerbates Aβ accumulation and promotes cellular senescence in a mouse model of amyloidosis.Immunity & ageing : I & A · 2026Article
- Brain-wide induction of ΔFOSB and altered co-activation networks in a rat model for exercise training.Translational psychiatry · 2026Article
- Kv4.2The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Altered Physiology and Ensemble Recruitment of Dentate Gyrus Semilunar Granule Cells in a Mouse Model of Epilepsy.bioRxiv : the preprint server for biology · 2026Article
- Article
- Multiomic Analyses Reveal Brainstem Metabolic Changes in a Mouse Model of Dravet Syndrome.Cells · 2025Article
- Restoration of sFRP3 Preserves the Neural Stem Cell Pool and Spatial Discrimination Ability in a Mouse Model of Alzheimer's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- FGF10 ameliorates epileptic seizures and related cognitive dysfunction via the FGFR2/CALB1 signaling pathway.Journal of translational medicine · 2025Article
- Remote spatial memory deficits in mouse models of neuropsychiatric disorders with immature dentate gyrus phenotype.The international journal of neuropsychopharmacology · 2025Article
- Transcriptomic analyses of human brains with Alzheimer's disease identified dysregulated epilepsy-causing genes.Epilepsy & behavior : E&B · 2025Article
- Increased excitability of dentate gyrus mossy cells occurs early in life in the Tg2576 model of Alzheimer's disease.Alzheimer's research & therapy · 2025Article
- Article
- Persistent ∆FosB expression limits recurrent seizure activity and provides neuroprotection in the dentate gyrus of APP mice.Progress in neurobiology · 2024Article
13 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 7 institutions in 1 country.
Funding
Abstract
The calcium-binding protein calbindin-D28k is critical for hippocampal function and cognition, but its expression is markedly decreased in various neurological disorders associated with epileptiform activity and seizures. In Alzheimer's disease (AD) and epilepsy, both of which are accompanied by recurrent seizures, the severity of cognitive deficits reflects the degree of calbindin reduction in the hippocampal dentate gyrus (DG). However, despite the importance of calbindin in both neuronal physiology and pathology, the regulatory mechanisms that control its expression in the hippocampus are poorly understood. Here we report an epigenetic mechanism through which seizures chronically suppress hippocampal calbindin expression and impair cognition. We demonstrate that ΔFosB, a highly stable transcription factor, is induced in the hippocampus in mouse models of AD and seizures, in which it binds and triggers histone deacetylation at the promoter of the calbindin gene (Calb1) and downregulates Calb1 transcription. Notably, increasing DG calbindin levels, either by direct virus-mediated expression or inhibition of ΔFosB signaling, improves spatial memory in a mouse model of AD. Moreover, levels of ΔFosB and calbindin expression are inversely related in the DG of individuals with temporal lobe epilepsy (TLE) or AD and correlate with performance on the Mini-Mental State Examination (MMSE). We propose that chronic suppression of calbindin by ΔFosB is one mechanism through which intermittent seizures drive persistent cognitive deficits in conditions accompanied by recurrent seizures.
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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.