ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2024
Progressive reduction of nuclear receptor Nr4a1 mediates age-dependent cognitive decline.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 15 citations in OpenAlex.
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- Targeting enhancing myelin regeneration reverses cognitive deficits in a mouse model of intellectual disability.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
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- ANKRD1 sustains a neurogenic BMSC niche and counters cognitive aging.International journal of oral science · 2026Article
- Age-dependent elevation of Nr4a1 attenuates PI3K/AKT/GSK3β pathway and mediates tau hyperphosphorylation and cognitive impairments.Journal of advanced research · 2026Article
- Nr4a1 regulates microglia overactivation-mediated neuroinflammation to ameliorate cognitive impairment in trigeminal neuralgia rats.The journal of headache and pain · 2026Article
- Peripheral blood microarray-based transcriptomic and epigenetic analyses identify immune, inflammation, and metabolic dysregulation in Alzheimer's disease.NPJ dementia · 2026Article
- Memory-Associated Immediate Early Genes: Roles in Synaptic Function, Memory Processes, and Neurological Diseases.Molecular neurobiology · 2025Review
- Opposing roles of microglial and macrophagic C3ar1 signaling in stress-induced synaptic and behavioral changes.Molecular psychiatry · 2025Article
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- Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventions.Signal transduction and targeted therapy · 2025Review
- MeCP2 Lactylation Protects against Ischemic Brain Injury by Transcriptionally Regulating Neuronal Apoptosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Analysis and Identification of Therapeutic Targets for Neuronal Regeneration After Ischemic Stroke.Brain and behavior · 2025Article
- Progressive reduction of nuclear receptor Nr4a1 mediates age-dependent cognitive decline.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
introductionCognitive decline progresses with age, and Nr4a1 has been shown to participate in memory functions. However, the relationship between age-related Nr4a1 reduction and cognitive decline is undefined.
methodsNr4a1 expressions were evaluated by quantitative PCR and immunochemical approaches. The cognition of mice was examined by multiple behavioral tests. Patch-clamp experiments were conducted to investigate the synaptic function.
resultsNR4A1 in peripheral blood mononuclear cells decreased with age in humans. In the mouse brain, age-dependent Nr4a1 reduction occurred in the hippocampal CA1. Deleting Nr4a1 in CA1 pyramidal neurons (PyrNs) led to the impairment of cognition and excitatory synaptic function. Mechanistically, Nr4a1 enhanced TrkB expression via binding to its promoter. Blocking TrkB compromised the cognitive amelioration with Nr4a1-overexpression in CA1 PyrNs. DISCUSSION: Our results elucidate the mechanism of Nr4a1-dependent TrkB regulation in cognition and synaptic function, indicating that Nr4a1 is a target for the treatment of cognitive decline. HIGHLIGHTS: Nr4a1 is reduced in PBMCs and CA1 PyrNs with aging. Nr4a1 ablation in CA1 PyrNs impaired cognition and excitatory synaptic function. Nr4a1 overexpression in CA1 PyrNs ameliorated cognitive impairment of aged mice. Nr4a1 bound to TrkB promoter to enhance transcription. Blocking TrkB function compromised Nr4a1-induced cognitive improvement.
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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.