ArticleProceedings of the National Academy of Sciences of the United States of America2022
Targeting acetyl-CoA metabolism attenuates the formation of fear memories through reduced activity-dependent histone acetylation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 40 citations in OpenAlex.
- Acetyl-CoA-dependent processes are preferentially supported by local metabolite synthesis.Science advances · 2026Article
- Epigenetic landscapes of classical psychedelics and ketamine: molecular mechanisms of long-lasting neuromodulation.Molecular psychiatry · 2026Review
- Ablation of ACSS2 drives alteration to cardiac and hepatic proteomic landscapes in a tissue- and sex-specific manner.Journal of proteomics · 2026Article
- Trifluoperazine upregulates ACSS2-related autophagy and promotes cerebral cognitive function in rats after sleep deprivation.iScience · 2026Article
- Acetate enhances long-term memory in female mice by sex-, context-, and brain region-specific epigenetic and transcriptional remodeling.Science signaling · 2026Article
- Mitochondrial CaNature metabolism · 2026Article
- ACSS2 upregulation enhances neuronal resilience to aging and tau-associated neurodegeneration.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Study on the cognitive effects of eye movement desensitization and reprocessing: proposed active mechanisms.Frontiers in computational neuroscience · 2026Article
- TCA-cycle metabolites in the nucleus: drivers of chromatin and epigenetic control.BMC biology · 2025Review
- ACSS2 involved in acetyl-CoA synthesis regulates skeletal muscle function.FEBS letters · 2025Article
- Detecting ALDH2 activity in live cellsChemical science · 2025Article
- Neural Metabolic Networks: Key Elements of Healthy Brain Function.Journal of neurochemistry · 2025Review
- Bridging epigenomics and tumor immunometabolism: molecular mechanisms and therapeutic implications.Molecular cancer · 2025Review
- Decreased voluntary alcohol intake and ventral striatal epigenetic and transcriptional remodeling in male Acss2 KO mice.Neuropharmacology · 2025Article
- Stress Molecular Signaling in Interaction With Cognition.Biological psychiatry · 2025Review
- Molecular Targets and Small Molecules Modulating Acetyl Coenzyme A in Physiology and Diseases.ACS pharmacology & translational science · 2025Review
- Basic Epigenetic Mechanisms.Sub-cellular biochemistry · 2025Review
- Theoretical framework for the difference of two negative binomial distributions and its application in comparative analysis of sequencing data.Genome research · 2024Article
- ALDH1A3-acetaldehyde metabolism potentiates transcriptional heterogeneity in melanoma.Cell reports · 2024Article
- Histone acetylation in an Alzheimer's disease cell model promotes homeostatic amyloid-reducing pathways.Acta neuropathologica communications · 2024Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
Histone acetylation is a key component in the consolidation of long-term fear memories. Histone acetylation is fueled by acetyl-coenzyme A (acetyl-CoA), and recently, nuclear-localized metabolic enzymes that produce this metabolite have emerged as direct and local regulators of chromatin. In particular, acetyl-CoA synthetase 2 (ACSS2) mediates histone acetylation in the mouse hippocampus. However, whether ACSS2 regulates long-term fear memory remains to be determined. Here, we show that Acss2 knockout is well tolerated in mice, yet the Acss2-null mouse exhibits reduced acquisition of long-term fear memory. Loss of Acss2 leads to reductions in both histone acetylation and expression of critical learning and memory-related genes in the dorsal hippocampus, specifically following fear conditioning. Furthermore, systemic administration of blood-brain barrier-permeable Acss2 inhibitors during the consolidation window reduces fear-memory formation in mice and rats and reduces anxiety in a predator-scent stress paradigm. Our findings suggest that nuclear acetyl-CoA metabolism via ACSS2 plays a critical, previously unappreciated, role in the formation of fear memories.
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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.