The cold-inducible RNA-binding protein-Thioredoxin 1 pathway ameliorates mitochondrial dysfunction and mitochondrial dynamin-related protein 1 level in the hippocampus of aged mice with perioperative neurocognitive dysfunction.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37641878", "kind": "science-record", "revision": 5, "content_hash": "sha256:ff7492f12a9a8f8116d702687c7a58015ecbfd9949f792715b0ce6795a0b5264", "created_at": "2026-11-01T19:02:25Z", "updated_at": "2026-11-01T22:52:36Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "The cold-inducible RNA-binding protein-Thioredoxin 1 pathway ameliorates mitochondrial dysfunction and mitochondrial dynamin-related protein 1 level in the hippocampus of aged mice with perioperative neurocognitive dysfunction.", "doi": "10.1111/cns.14433", "pmid": "37641878", "authors": ["Jingyao Huang", "Yongliang Zhu", "Yongxin Liu", "Rui Zhang", "Zhenjiang Zhang", "Jie Liu", "Zhihao Zhang", "Yingxia Liang", "Baoyu Ma"], "journal": "CNS neuroscience & therapeutics", "year": 2024, "abstract": "BACKGROUND: As a multi-disease model, neuroinflammation, mitochondrial dysfunction, and oxidative stress might be involved in the pathogenic process of perioperative neurocognitive dysfunction (PND). Dynamin-related protein 1 (Drp1) could mediate mitochondrial fission and play important roles in mitochondrial dynamic homeostasis and mitochondria function. The Drp1 may be involved in PND development. The cold-inducible RNA-binding protein (Cirbp) could bind to the 3'-UTR of the thioredoxin 1 (Trx1) mRNA, control oxidative stress, and improve mitochondrial function. In this study, we hypothesized that the Cirbp-Trx1 pathway could ameliorate mitochondrial dysfunction and Drp1 levels in PND mice.\nMETHODS: Differentially expressed genes were screened using the Gene Expression Omnibus (GEO) database GSE95426 and validated using PCR. Eighteen-month-old C57BL/6 mice were subjected to tibial fracture surgery to generate a PND model. Cirbp was upregulated by hippocampal stereotaxic injections of over-Cirbp plasmid according to the manufacturer's instructions for the in vivo DNA transfection reagent. Cirbp expression was measured using western blot (WB) and immunofluorescence (IF). The Morris water maze (MWM) was used to assess cognitive function. After behavioral testing, the hippocampal tissue was extracted to examine changes in mitochondrial Drp1, mitochondrial function, neuroinflammation, and oxidative stress.\nRESULTS: Differential gene screening showed that Cirbp expression was significantly downregulated (fold change >1.5, p = 0.003272) in the PND model. In this study, we also found that Cirbp protein levels were downregulated, accompanied by an impairment of cognition, a decrease in superoxide dismutase (SOD) activity, and an increase in malondialdehyde (MDA) content, mitochondrial Drp1 levels, neuroinflammation, and apoptosis. Cirbp overexpression increased Trx1 protein levels and reversed the damage. However, this protective effect was abolished by PX-12 treatment with a Trx1 inhibitor.\nCONCLUSIONS: The Cirbp-Trx1 pathway may regulate mitochondrial dysfunction and mitochondrial Drp1 expression in the hippocampus of PND mice to ameliorate cognitive dysfunction.", "claims": [{"id": "claim-method", "statement": "The qRT‐PCR results were analyzed using unpaired Student's t‐tests, and data between multiple groups were analyzed using one‐way ANOVA followed by Tukey's post‐hoc test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37641878", "locator": "sections[18] \"Statistical analysis\" paragraph 2", "quote": "The qRT‐PCR results were analyzed using unpaired Student's t‐tests, and data between multiple groups were analyzed using one‐way ANOVA followed by Tukey's post‐hoc test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data about this study are included in the article, and further inquiries can be directed to the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37641878", "locator": "sections[32] \"DATA AVAILABILITY STATEMENT\" paragraph 2", "quote": "All data about this study are included in the article, and further inquiries can be directed to the corresponding authors."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The Cirbp‐Trx1 pathway may regulate mitochondrial dysfunction and mitochondrial Drp1 expression in the hippocampus of PND mice to ameliorate cognitive dysfunction.", "kind": "quantitative", "target": {"value": 0.003272, "unit": "p-value", "tolerance": null, "source": "Differential gene screening showed that Cirbp expression was significantly downregulated (fold change >1.5, p = 0.003272) in the PND model."}, "evidence": [{"asset": "source:pmid:37641878", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "The Cirbp‐Trx1 pathway may regulate mitochondrial dysfunction and mitochondrial Drp1 expression in the hippocampus of PND mice to ameliorate cognitive dysfunction."}, {"asset": "source:pmid:37641878", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Differential gene screening showed that Cirbp expression was significantly downregulated (fold change >1.5, p = 0.003272) in the PND model."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The Cirbp‐Trx1 pathway may regulate mitochondrial dysfunction and mitochondrial Drp1 expression in the hippocampus of PND mice to ameliorate cognitive dysfunction.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:37641878"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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Eighteen-month-old C57BL/6 mice were subjected to tibial fracture surgery to gene", "g to the manufacturer's instructions for the in vivo DNA transfection reagent. Cirbp expression w", "fracture surgery. One day after surgery, all mice were sacrificed, and total hippocampal RNA was extracted to", "al Centre of Weifang Medical University. The mice were housed in an environment of temperature and"], "order_basis": "paper_text_order:1049", "id": "assay:1"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.85, "evidence": ["ufacturer's instructions for the in vivo DNA transfection reagent. Cirbp expression was measured using"], "order_basis": "paper_text_order:1268", "id": "assay:2"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["reagent. Cirbp expression was measured using western blot (WB) and immunofluorescence (IF). The Morris", "l Cirbp and Trx1 expression were detected by western blot (WB) and immunofluorescence (IF). For the be"], "order_basis": "paper_text_order:1326", "id": "assay:3"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ion was measured using western blot (WB) and immunofluorescence (IF). The Morris water maze (MWM) was used t", "ssion were detected by western blot (WB) and immunofluorescence (IF). For the behavioral test, the mice firs", "teral stereotaxic delivery of over‐Cirbp and immunostaining for Cirbp (green). (C) Volcanic plot of mRNA"], "order_basis": "paper_text_order:1348", "id": "assay:4"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.69, "evidence": ["hondrial Drp1 levels, neuroinflammation, and apoptosis. 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