Academic Journal
Transcriptomic characterization of prefrontal cortical remodeling and glutamate changes detected by Glu-CEST MRI in rats with propofol-induced neuroadaptations.
| Τίτλος: | Transcriptomic characterization of prefrontal cortical remodeling and glutamate changes detected by Glu-CEST MRI in rats with propofol-induced neuroadaptations. |
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| Συγγραφείς: | Huang Z; Department of Radiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China; Laboratory of Medical Molecular Imaging & Laboratory of Molecular Cardiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China., Zhuang Z; Department of Radiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China; Laboratory of Medical Molecular Imaging & Laboratory of Molecular Cardiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China., Huang Y; Department of Radiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China; Laboratory of Medical Molecular Imaging & Laboratory of Molecular Cardiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China., Shi X; Department of Radiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China., Guo B; Department of Radiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China; Laboratory of Medical Molecular Imaging & Laboratory of Molecular Cardiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China., Xu Z; Department of Radiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China; Laboratory of Medical Molecular Imaging & Laboratory of Molecular Cardiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China., Chen Y; Department of Radiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China; Laboratory of Medical Molecular Imaging & Laboratory of Molecular Cardiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China., Cao Y; Department of Radiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China; Laboratory of Medical Molecular Imaging & Laboratory of Molecular Cardiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China., Zheng Y; Department of Radiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China; Laboratory of Medical Molecular Imaging & Laboratory of Molecular Cardiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China., Xie L; Department of Radiology, The Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, 515041, China. Electronic address: 13lxie1@stu.edu.cn., Wu R; Department of Radiology, The Second Affiliated Hospital of Shantou University Medical College, Shantou, China. Electronic address: hwu@stu.edu.cn., Ma S; Department of Radiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China; Laboratory of Medical Molecular Imaging & Laboratory of Molecular Cardiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China. Electronic address: shma@stu.edu.cn. |
| Πηγή: | Neurochemistry international [Neurochem Int] 2026 Oct; Vol. 199, pp. 106227. Date of Electronic Publication: 2026 Jul 20. |
| Τύπος έκδοσης: | Journal Article; Research Support, Non-U.S. Gov't |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Pergamon Press Country of Publication: England NLM ID: 8006959 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-9754 (Electronic) Linking ISSN: 01970186 NLM ISO Abbreviation: Neurochem Int Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Oxford [Elmsford, N. Y.] Pergamon Press. |
| Ιατρικοί όροι (MeSH): | Propofol*/pharmacology , Propofol*/administration & dosage , Prefrontal Cortex*/drug effects , Prefrontal Cortex*/metabolism , Prefrontal Cortex*/diagnostic imaging , Glutamic Acid*/metabolism , Transcriptome*/drug effects , Transcriptome*/physiology , Magnetic Resonance Imaging*/methods , Anesthetics, Intravenous*/administration & dosage , Anesthetics, Intravenous*/pharmacology , Adaptation, Physiological*/drug effects , Adaptation, Physiological*/physiology , Neuronal Plasticity*/drug effects , Neuronal Plasticity*/physiology, Animals ; Rats ; Male ; Rats, Sprague-Dawley |
| Περίληψη: | Propofol, a widely used intravenous anesthetic, carries an underrecognized risk of abuse and dependence; however, the prefrontal cortical molecular alterations and in vivo glutamatergic changes associated with propofol-induced neuroadaptations remain poorly characterized. The present study established a rat model of intravenous propofol self-administration (SA) using a fixed-ratio 1 (FR1) reinforcement schedule over 14 consecutive days. Behavioral validation via the open field test (OFT) demonstrated that propofol-exposed rats exhibited significantly enhanced spontaneous locomotor activity and attenuated anxiety-like states following training. RNA sequencing of prefrontal cortical tissue identified 174 differentially expressed genes (DEGs), with downregulated genes (n = 133) substantially predominating over upregulated ones (n = 41). Gene enrichment analysis revealed that upregulated DEGs were significantly enriched in pathways associated with oxidative stress injury, nitric oxide signaling, and hemoglobin-related oxygen metabolism, while downregulated DEGs were enriched in neuropeptide signaling pathways, responsive to psychostimulants and neurodegenerative disease, collectively suggesting a broad-scale inhibitory transcriptional remodeling of the prefrontal cortex under chronic propofol exposure. Glu-CEST MRI at 7.0T revealed a significant whole-brain elevation of glutamate levels in propofol-exposed rats relative to saline controls, with a particularly pronounced region-specific increase in the motor cortex, indicating there exists a disorder characterized by abnormal glutamate regulation within the central nervous system. These findings provide a multidimensional molecular and neuroimaging characterization of chronic propofol administration, identifying prefrontal cortical oxidative stress, neuropeptide system suppression, and dysregulated glutamate signaling as candidate pathological substrates, and highlighting Glu-CEST imaging as a promising non-invasive biomarker for anesthetic abuse. (Copyright © 2026 The Authors. Published by Elsevier Ltd.. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare no competing interests. |
| Contributed Indexing: | Keywords: Glu-CEST MRI; Intravenous self-administration; Prefrontal cortex; Propofol; RNA sequencing |
| Substance Nomenclature: | YI7VU623SF (Propofol) 3KX376GY7L (Glutamic Acid) 0 (Anesthetics, Intravenous) |
| Entry Date(s): | Date Created: 20260720 Date Completed: 20260815 Latest Revision: 20260922 |
| Update Code: | 20260923 |
| DOI: | 10.1016/j.neuint.2026.106227 |
| PMID: | 42476461 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1872-9754 |
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| DOI: | 10.1016/j.neuint.2026.106227 |