ArticleCell reports2023
Circadian protein TIMELESS regulates synaptic function and memory by modulating cAMP signaling.
Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 15 citations in OpenAlex.
- Defining Clock Neurons Within Distributed Circadian Circuits Through Multiscale Technologies.Journal of biological rhythms · 2026Review
- Circadian rhythm disruption alters rhythmic properties of clock and memory gene expression in the hippocampi of rats.bioRxiv : the preprint server for biology · 2026Article
- The ASD Risk GenebioRxiv : the preprint server for biology · 2026Article
- PDE4 inhibitor rolipram dynamically regulates the balance between D1-MSNs and D2-MSNs in the DMS to modulate abnormal "Go" behavior associated with alcohol addiction.Acta pharmacologica Sinica · 2026Article
- Circ_0049472 downregulation relieves Amyloid-β-induced neuronal injury by modulating PDE4A expression via targeting miR-22-3p in Alzheimer's disease.Metabolic brain disease · 2025Article
- Protective effect of PDE4B subtype-specific inhibition in an App knock-in mouse model for Alzheimer's disease.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Identification of diagnostic markers related to inflammatory response and cellular senescence in endometriosis using machine learning and in vitro experiment.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- Targeting the circadian modulation: novel therapeutic approaches in the management of ASD.Frontiers in psychiatry · 2024Review
- An integrative evaluation of circadian gene TIMELESS as a pan-cancer immunological and predictive biomarker.European journal of medical research · 2023Article
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
The regulation of neurons by circadian clock genes is thought to contribute to the maintenance of neuronal functions that ultimately underlie animal behavior. However, the impact of specific circadian genes on cellular and molecular mechanisms controlling synaptic plasticity and cognitive function remains elusive. Here, we show that the expression of the circadian protein TIMELESS displays circadian rhythmicity in the mammalian hippocampus. We identify TIMELESS as a chromatin-bound protein that targets synaptic-plasticity-related genes such as phosphodiesterase 4B (Pde4b). By promoting Pde4b transcription, TIMELESS negatively regulates cAMP signaling to modulate AMPA receptor GluA1 function and influence synaptic plasticity. Conditional deletion of Timeless in the adult forebrain impairs working and contextual fear memory in mice. These cognitive phenotypes were accompanied by attenuation of hippocampal Schaffer-collateral synapse long-term potentiation. Together, these data establish a neuron-specific function of mammalian TIMELESS by defining a mechanism that regulates synaptic plasticity and cognitive function.
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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.