ArticleNeurotoxicity research2016
Hypermethylation of Hippocampal Synaptic Plasticity-Related genes is Involved in Neonatal Sevoflurane Exposure-Induced Cognitive Impairments in Rats.
Article in Neurotoxicity research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- Dexmedetomidine Mitigates Sevoflurane-Induced Neurodevelopmental Effects in Paediatric Anaesthesia: A Meta-Analysis and Preclinical Study.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026Pooled it
- Mechanisms of natural compounds in treating inhalation anesthesia-induced cognitive dysfunction.Frontiers in pharmacology · 2026Review
- Perioperative neurocognitive disorders: Advances in molecular mechanisms and bioactive molecules.Ageing research reviews · 2025Review
- Deciphering sevoflurane-induced neurotoxicity: from isolated targets to intricate regulatory networks.Frontiers in neuroscience · 2025Review
- General anesthesia induces acute cell-free DNA methylation changes in peripheral blood.Journal of thoracic disease · 2024Article
- DNA methylation, histone acetylation in the regulation of memory and its modulation during aging.Frontiers in aging · 2024Review
- Ketamine counteracts sevoflurane-induced depressive-like behavior and synaptic plasticity impairments through the adenosine A2A receptor/ERK pathway in rats.Molecular neurobiology · 2023Article
- Sevoflurane Exposure in Neonates Perturbs the Expression Patterns of Specific Genes That May Underly the Observed Learning and Memory Deficits.International journal of molecular sciences · 2023Article
- Intergenerational Perioperative Neurocognitive Disorder.Biology · 2023Review
- General Anesthesia in Early Childhood Significantly Reduces Asthma Incidence and Clinical Visits: A Nationwide Population-Based Cohort Study.Children (Basel, Switzerland) · 2023Article
- Minocycline Attenuates Sevoflurane-Induced Postoperative Cognitive Dysfunction in Aged Mice by Suppressing Hippocampal Apoptosis and the Notch Signaling Pathway-Mediated Neuroinflammation.Brain sciences · 2023Article
- Postnatal GABAMolecular neurobiology · 2022Article
- The Role of Epigenetic Modifications in Neurotoxicity Induced by Neonatal General Anesthesia.Frontiers in molecular neuroscience · 2022Review
- Research progress on molecular mechanisms of general anesthetic-induced neurotoxicity and cognitive impairment in the developing brain.Frontiers in neurology · 2022Review
- Neonatal anesthesia and dysregulation of the epigenome†.Biology of reproduction · 2021Review
- The potential role of stress and sex steroids in heritable effects of sevoflurane†.Biology of reproduction · 2021Review
- Inhibition of RhoA Activity Does Not Rescue Synaptic Development Abnormalities and Long-Term Cognitive Impairment After Sevoflurane Exposure.Neurochemical research · 2021Article
- Neonatal Sevoflurane Exposure Impairs Learning and Memory by the Hypermethylation of Hippocampal Synaptic Genes.Molecular neurobiology · 2021Article
- Gene-Specific DNA Methylation Linked to Postoperative Cognitive Dysfunction in Apolipoprotein E3 and E4 Mice.Journal of Alzheimer's disease : JAD · 2021Article
- Effects of Sevoflurane Exposure During Late Pregnancy on Brain Development and Beneficial Effects of Enriched Environment on Offspring Cognition.Cellular and molecular neurobiology · 2020Article
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
General anesthetics given to immature rodents cause delayed neurobehavioral abnormalities via incompletely understood mechanisms. DNA methylation, one of the epigenetic modifications, is essential for the modulation of hippocampal synaptic plasticity through regulating the related genes. Therefore, we investigated whether abnormalities in the hippocampal DNA methylation of synaptic plasticity-related genes are involved in neonatal sevoflurane exposure-induced cognitive impairments in rats. Male Sprague-Dawley rats were exposed to 3 % sevoflurane or 30 % oxygen/air for 2 h daily from postnatal day 7 (P7) to P9 and were treated with DNA methyltransferases (DNMTs) inhibitor 5-aza-2-deoxycytidine (5-AZA) or vehicle 1 h before the first sevoflurane exposure on P7. The rats were euthanized 1, 6, 24 h, and 30 days after the last sevoflurane exposure, and the brain tissues were harvested for biochemical analysis. Cognitive functions were evaluated by the open field, fear conditioning, and Morris water maze (MWM) tests on P39, P41-43, and P50-57, respectively. In the present study, repeated neonatal sevoflurane exposure resulted in hippocampus-dependent cognitive impairments as assessed by fear conditioning and MWM tests. The cognitive impairments were associated with the increased DNMTs and hypermethylation of brain-derived neurotrophic factor (BDNF) and Reelin genes, and subsequent down-regulation of BDNF and Reelin genes, which finally led to the decrease of dendritic spines in the hippocampal pyramidal neurons in adolescent rats. Notably, pretreatment with 5-AZA reversed these sevoflurane-induced abnormalities. In conclusion, our results suggest that hypermethylation of hippocampal BDNF and Reelin is involved in neonatal sevoflurane exposure-induced cognitive impairments.
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