Academic Journal
Neonatal propofol exposure induces region-specific neurotoxic proteomic signatures in mouse cortex and hippocampus.
| Τίτλος: | Neonatal propofol exposure induces region-specific neurotoxic proteomic signatures in mouse cortex and hippocampus. |
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| Συγγραφείς: | Chen L; Department of Anesthesiology, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361003, China; Department of Anesthesiology, Department of Pediatrics, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China., Wang H; Department of Anesthesiology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050010, China., Huang H; Department of Anesthesiology, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361003, China., Lin Y; Department of Anesthesiology, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361003, China., Gao H; Department of Anesthesiology, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361003, China. Electronic address: gaohaiying@xmu.edu.cn. |
| Πηγή: | Brain research [Brain Res] 2026 Oct 15; Vol. 1889, pp. 150477. Date of Electronic Publication: 2026 Jul 23. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier/North-Holland Biomedical Press Country of Publication: Netherlands NLM ID: 0045503 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-6240 (Electronic) Linking ISSN: 00068993 NLM ISO Abbreviation: Brain Res Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Amsterdam Elsevier/North-Holland Biomedical Press. |
| Ιατρικοί όροι (MeSH): | Propofol*/pharmacology , Propofol*/toxicity , Hippocampus*/drug effects , Hippocampus*/metabolism , Cerebral Cortex*/drug effects , Cerebral Cortex*/metabolism, Proteomics/methods ; Exosomes/metabolism ; Exosomes/drug effects ; Proteome/metabolism ; Animals ; Mice, Inbred C57BL ; Mice ; Animals, Newborn ; Male ; Female |
| Περίληψη: | Neonatal propofol exposure has been implicated in long-term neurodevelopmental impairments; however, region-specific molecular mechanisms remain unclear. This study examined region-specific proteomic alterations in exosome-enriched small extracellular vesicles (exosome-enriched sEVs) from the cortex and hippocampus induced by neonatal propofol exposure. Using a clinically relevant repeated-dose regimen, C57BL/6 mice received propofol (50 mg/kg, P5-P7). At P21, exosome-enriched sEVs were isolated and analyzed by data-independent acquisition mass spectrometry. Candidate differentially expressed proteins (candidate DEPs) were defined by fold change (FC) ≥ 1.5 or ≤ 0.667 and nominal p < 0.05, followed by Gene Ontology (GO), KEGG pathways, Cluster of Orthologous Groups (COG), and domain enrichment analyses. After Benjamini-Hochberg correction, no protein reached q < 0.05, indicating that the exploratory findings were not significant. We identified 63 candidate DEPs in the hippocampus and 55 in the cortex. Hippocampal downregulated proteins enriched in synaptic vesicle cycling, oxidative phosphorylation, and apoptosis, suggesting synaptic-mitochondrial disruption; upregulated proteins associated with ER stress and chaperone-mediated autophagy, suggesting proteostatic adaptation. Cortical candidate DEPs reflected suppressed mitochondrial function alongside enhanced translation and cytoskeletal remodeling. These region- and direction-specific changes were consistently observed across all bioinformatic platforms. The hippocampus showed pronounced synaptic and mitochondrial alterations, while the cortex exhibited cytoskeletal changes and metabolic shifts. In conclusion, Propofol induces distinct neurotoxic proteomic signatures in the neonatal hippocampus and cortex, suggesting compartment-specific vulnerability and compensatory remodeling. Thus, exosome-enriched sEV proteomics offers a sensitive approach to detecting early anesthetic-induced neurodevelopmental disturbances. (Copyright © 2026. Published by Elsevier B.V.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: Candidate differentially expressed proteins (candidateDEPs); Cortex; Exosome-enrichedsEV proteomics; Hippocampus; Neonatal brain; Neurotoxicity; Propofol |
| Substance Nomenclature: | YI7VU623SF (Propofol) 0 (Proteome) |
| Entry Date(s): | Date Created: 20260723 Date Completed: 20260808 Latest Revision: 20260808 |
| Update Code: | 20260809 |
| DOI: | 10.1016/j.brainres.2026.150477 |
| PMID: | 42492603 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1872-6240 |
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| DOI: | 10.1016/j.brainres.2026.150477 |