Academic Journal
Inhibition of the IRE1α/ASK1/JNK signaling pathway ameliorates perioperative neurocognitive disorder in aged mice following abdominal surgery.
| Τίτλος: | Inhibition of the IRE1α/ASK1/JNK signaling pathway ameliorates perioperative neurocognitive disorder in aged mice following abdominal surgery. |
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| Συγγραφείς: | Zhang W; Department of Anesthesiology, Perioperative and Pain Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China., Liu C; Department of Anesthesiology, Perioperative and Pain Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China., Xu R; Department of Anesthesiology, Fuyang People's Hospital, Fuyang, China., Li Z; Department of Anesthesiology, Perioperative and Pain Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China., Xu Y; Department of Anesthesiology, Perioperative and Pain Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China., Yin J; Department of Anesthesiology, Perioperative and Pain Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China., Han F; Department of Surgery, Lianshui County People's Hospital, Huai'an, China., Meng Q; School of Medicine, Nanjing University of Chinese Medicine, Nanjing, China., Duan M; Department of Anesthesiology, Nanjing Tianyinshan Hospital, The First Affiliated Hospital of China Pharmaceutical University, Nanjing, China; Department of Anesthesiology, Nanjing BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, China. Electronic address: dml9001@nju.edu.cn., Zhang Z; School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China.. Electronic address: zzy@njmu.edu.cn., Wang X; Department of Anesthesiology, Perioperative and Pain Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China. Electronic address: wxl145381@njmu.edu.cn. |
| Πηγή: | Brain research [Brain Res] 2026 Oct 01; Vol. 1888, pp. 150397. Date of Electronic Publication: 2026 Jun 01. |
| 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): | Endoribonucleases*/metabolism , Endoribonucleases*/antagonists & inhibitors , Protein Serine-Threonine Kinases*/metabolism , Protein Serine-Threonine Kinases*/antagonists & inhibitors , MAP Kinase Kinase Kinase 5*/metabolism , MAP Kinase Signaling System*/drug effects , MAP Kinase Signaling System*/physiology , Neurocognitive Disorders*/metabolism , Neurocognitive Disorders*/etiology , Postoperative Cognitive Complications*/metabolism, Endoplasmic Reticulum Stress/physiology ; Endoplasmic Reticulum Stress/drug effects ; Hippocampus/metabolism ; Abdomen/surgery ; Aging/metabolism ; Animals ; Mice ; Male ; Mice, Inbred C57BL ; Signal Transduction ; Disease Models, Animal |
| Περίληψη: | Background: Perioperative neurocognitive disorder (PND) is a common postoperative complication, although its pathophysiological mechanisms remain incompletely understood. Inositol-requiring enzyme 1α (IRE1α) is an endoplasmic reticulum (ER) membrane sensor that participates in the pathogenesis of cognitive disorders through ER stress. However, its relationship with PND remains unclear. This study aimed to investigate whether IRE1α contributes to PND through surgery-induced ER stress. Methods: An abdominal surgery model was used to investigate the postoperative effects of surgery on the mouse hippocampus. Behavioral tests, mRNA sequencing of hippocampal tissue, protein detection, Nissl staining, immunohistochemistry, immunofluorescence staining, and electron microscopy were performed. Aged mice in the surgery group received intraperitoneal injection of an IRE1α inhibitor. Results: Surgery-induced cognitive impairment was mainly observed in aged mice. Surgery-induced ER stress was associated with activation of the IRE1α/ASK1/JNK pathway, increased microglial activation, enhanced release of inflammatory factors, and mitochondrial damage. Treatment with the IRE1α inhibitor improved these outcomes. Conclusion: Surgery-induced ER stress was associated with IRE1α overactivation and postoperative cognitive impairment in aged mice. Suppression of the IRE1α/ASK1/JNK pathway ameliorated postoperative neuroinflammation, mitochondrial pathology, and microglial activation, thereby improving postoperative cognitive function in aged mice. (Copyright © 2026 Elsevier B.V. All rights reserved.) |
| 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: Abdominal surgery; Endoplasmic reticulum stress; Inositol-requiring enzyme 1α; Microglia; Neuroinflammation; Perioperative neurocognitive disorder |
| Substance Nomenclature: | EC 3.1.- (Endoribonucleases) EC 2.7.11.1 (Ern1 protein, mouse) EC 2.7.11.1 (Protein Serine-Threonine Kinases) EC 2.7.11.25 (MAP Kinase Kinase Kinase 5) |
| Entry Date(s): | Date Created: 20260602 Date Completed: 20260704 Latest Revision: 20260704 |
| Update Code: | 20260705 |
| DOI: | 10.1016/j.brainres.2026.150397 |
| PMID: | 42229696 |
| Βάση Δεδομένων: | MEDLINE |
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