ArticleJournal of advanced research2025
Neonatal sevoflurane exposures inhibits DHHC5-mediated palmitoylation of TfR1 in oligodendrocytes, leading to hypomyelination and neurological impairments.
Article in Journal of advanced research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Sevoflurane-induced disruption of critical period Arc signaling drives aberrant microglial synaptic pruning and cognitive deficits.Acta pharmacologica Sinica · 2026Article
- CX3CL1/CX3CR1-dependent microglial phagocytosis of oligodendrocyte precursor cells contributes to sevoflurane-induced myelination impairments in neonatal mice.Journal of neuroinflammation · 2026Article
- Fat on Fire: Disrupted Microglial Lipid Metabolism as a Driver of Anesthetic Neurotoxicity.Neuroscience bulletin · 2026Review
- Sodium Butyrate Attenuates Sevoflurane-Induced Impaired Myelination and Neurobehavioral Deficits in Neonatal Mice via the H3K9ac/BDNF/TrkB Pathway.CNS neuroscience & therapeutics · 2026Article
- From lipid modification to cell death: the diverse roles of S-palmitoylation in cell fate decisions.Cell communication and signaling : CCS · 2026Review
- S-palmitoylation in ferroptosis: molecular mechanisms, modulators, and interplay with autophagy.Apoptosis : an international journal on programmed cell death · 2026Review
- Iron Overload Mediates the Differential Cell Fate of Astrocytes from Neurons and Its Regulatory Mechanisms in Ischemic Stroke.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Metabolic Regulatory Networks in Ferroptosis During Alzheimer's Disease, Mechanisms of Glial Cell Action, and Pathological Correlations with Neuritic Plaques.International journal of general medicine · 2026Review
- Bioengineered human brain organoids and organ-on-chip platforms for exposure-aware assessment of developmental neurotoxicity induced by general anesthetics and sedatives.Frontiers in bioengineering and biotechnology · 2026Review
- Extracellular vesicle signatures from eye lavage as novel non-invasive biomarkers for hypoxic ischaemic insult-findings from a neonatal mouse model.Frontiers in medical technology · 2025Article
- Anesthesia-Induced Ferroptosis: Bidirectional Regulation and Molecular Mechanisms in Cardio-Cerebral Injury.Journal of inflammation research · 2025Review
- Deciphering sevoflurane-induced neurotoxicity: from isolated targets to intricate regulatory networks.Frontiers in neuroscience · 2025Review
- Chloral Hydrate's Impact on Brain Development: From Clinical Safety to Molecular Mechanisms.Drug design, development and therapy · 2025Review
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Authors and funding
14 authors.
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Abstract
introductionNeonatal anesthesia-related neurological impairments are of significant concern, closely linked to oligodendrocyte dysfunction. However, there is a notable temporal discrepancy between the sustained development of oligodendrocytes (myelination) and the short-term vulnerability to anesthesia exposures.
objectivesGiven the significant rise in iron demand by oligodendrocytes during neonatal period, our objective was to clarify the potential roles and underlying mechanisms of iron homeostasis, particularly focusing on transferrin receptor 1 (TfR1), in governing the transient susceptibility to anesthesia.
methodsSevoflurane (3 %, 2 h/day) was administered to wildtype or Pdgfrα-Cre
resultsFollowing neonatal exposure to sevoflurane, the observed cognitive impairments and hypomyelination at P32 were attributed to iron accumulation and ferroptosis, particularly within oligodendrocytes of the corpus callosum (CC). This ferroptosis was mediated by enhanced endocytosis of transiently expressed TfR1, rather than its overexpression, due to inhibited palmitoylation. Among the 21 palmitoyltransferases, only Asp-His-His-Cys5 (DHHC5) was down-regulated in oligodendrocytes, reducing palmitoylation of TfR1 at the C98 cysteine site. Furthermore, specific overexpression of DHHC5 in oligodendrocytes significantly restored TfR1 endocytosis, hypomyelination, and ferroptosis, thereby preventing neuronal ferroptosis across multiple brain regions by decreasing iron transport, ultimately mitigating neurological impairments.
conclusionWe discovered that decreased DHHC5 in oligodendrocytes promotes TfR1 associated ferroptosis, resulting in hypomyelination and initiating neuronal ferroptosis, thereby impairing cognition following neonatal sevoflurane exposures. The transiently expressed TfR1 may mediate the critical period for neonatal anesthesia vulnerability. These findings highlight the pivotal role of TfR1-associated ferroptosis in neonatal anesthesia-associated neurotoxicity and oligodendrocyte-neuron interaction, while providing new perspect to understand temporary neurotoxicity of anesthesia. DHHC5 may represent promising therapeutic target to enhance the safety of neonatal anesthesia and iron-related oligodendrocytes disorders.
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