ArticleAnesthesiology2016
General Anesthesia Causes Epigenetic Histone Modulation of c-Fos and Brain-derived Neurotrophic Factor, Target Genes Important for Neuronal Development in the Immature Rat Hippocampus.
Article in Anesthesiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- General anesthesia in children and long-term neurodevelopmental deficits: A systematic review.Frontiers in molecular neuroscience · 2022Pooled it
- Effect of Different Anesthesia Methods on Emergence Agitation and Related Complications in Postoperative Patients with Osteosarcoma.Journal of healthcare engineering · 2021Trial
- Epigenetic Mechanisms in Perioperative Medicine: From Neuroinflammation and NETosis to Organ Dysfunction and Precision Therapeutics.Biomedicines · 2026Review
- Epigenetically driven impairment of BDNF-ARC signaling contributes to circadian and cognitive disarray in a mouse model of postoperative delirium.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Environmental exposures and epigenetic alterations in common chronic diseases: insights and challenges.Environmental epigenetics · 2026Review
- Anesthetic-induced epigenetic alterations: mechanisms and long-term clinical implications.Epigenetics · 2025Review
- Tenuifolin Attenuates Methamphetamine-Induced Reinstatement in Mice by Regulating Hippocampal Postsynaptic BDNF Signaling.CNS neuroscience & therapeutics · 2025Article
- The role of anesthesia in peri‑operative neurocognitive disorders: Molecular mechanisms and preventive strategies.Fundamental research · 2024Review
- Maternal upbringing and selective breeding for voluntary exercise behavior modify patterns of DNA methylation and expression of genes in the mouse brain.Genes, brain, and behavior · 2023Article
- Epigenetic and Anesthesia: Challenges and Opportunities.Anesthesiology and pain medicine · 2023Article
- Neonatal sevoflurane exposure induces long-term changes in dendritic morphology in juvenile rats and mice.Experimental biology and medicine (Maywood, N.J.) · 2023Article
- Association Between Receipt of General Anesthesia During Childhood and Attention Deficit Hyperactive Disorder and Neurodevelopment.Journal of Korean medical science · 2023Article
- Neonatal ketamine exposure impairs infrapyramidal bundle pruning and causes lasting increase in excitatory synaptic transmission in hippocampal CA3 neurons.Neurobiology of disease · 2022Article
- Epigenetic Mechanisms of Postoperative Cognitive Impairment Induced by Anesthesia and Neuroinflammation.Cells · 2022Review
- Isoflurane and Sevoflurane Induce Cognitive Impairment in Neonatal Rats by Inhibiting Neural Stem Cell Development Through Microglial Activation, Neuroinflammation, and Suppression of VEGFR2 Signaling Pathway.Neurotoxicity research · 2022Article
- Do We Have Viable Protective Strategies against Anesthesia-Induced Developmental Neurotoxicity?International journal of molecular sciences · 2022Review
- Metatranscriptomics Analysis Reveals Diverse Viral RNA in Cutaneous Papillomatous Lesions of Cattle.Evolutionary bioinformatics online · 2022Article
- Identification of Prefrontal Cortex and Amygdala Expressed Genes Associated With Sevoflurane Anesthesia on Non-human Primate.Frontiers in integrative neuroscience · 2022Article
- The Role of Epigenetic Modifications in Neurotoxicity Induced by Neonatal General Anesthesia.Frontiers in molecular neuroscience · 2022Review
- Neonatal anesthesia and dysregulation of the epigenome†.Biology of reproduction · 2021Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundEarly postnatal exposure to general anesthesia (GA) may be detrimental to brain development, resulting in long-term cognitive impairments. Older literature suggests that in utero exposure of rodents to GA causes cognitive impairments in the first-generation as well as in the second-generation offspring never exposed to GA. Thus, the authors hypothesize that transient exposure to GA during critical stages of synaptogenesis causes epigenetic changes in chromatin with deleterious effects on transcription of target genes crucial for proper synapse formation and cognitive development. They focus on the effects of GA on histone acetyltransferase activity of cAMP-responsive element-binding protein and the histone-3 acetylation status in the promoters of the target genes brain-derived neurotrophic factor and cellular Finkel-Biskis-Jinkins murine sarcoma virus osteosarcoma oncogene (c-Fos) known to regulate the development of neuronal morphology and function.
methodsSeven-day-old rat pups were exposed to a sedative dose of midazolam followed by combined nitrous oxide and isoflurane anesthesia for 6 h. Hippocampal neurons and organotypic hippocampal slices were cultured in vitro and exposed to GA for 24 h.
resultsGA caused epigenetic modulations manifested as histone-3 hypoacetylation (decrease of 25 to 30%, n = 7 to 9) and fragmentation of cAMP-responsive element-binding protein (two-fold increase, n = 6) with 25% decrease in its histone acetyltransferase activity, which resulted in down-regulated transcription of brain-derived neurotrophic factor (0.2- to 0.4-fold, n = 7 to 8) and cellular Finkel-Biskis-Jinkins murine sarcoma virus osteosarcoma oncogene (about 0.2-fold, n = 10 to 12). Reversal of histone hypoacetylation with sodium butyrate blocked GA-induced morphological and functional impairments of neuronal development and synaptic communication.
conclusionLong-term impairments of neuronal development and synaptic communication could be caused by GA-induced epigenetic phenomena.
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Registered trials
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