Gut-brain axis and exosome-mediated communication in postoperative cognitive dysfunction associated with colorectal cancerOA
Postoperative cognitive dysfunction(POCD)is a serious complication in patients undergoing colorectal cancer(CRC)surgery.It is characterized by significant impairments in memory,information processing and attention,and may also result in mood and personality changes,thereby increasing the risk of postoperative mortality.Currently,there are no effective interventions available,highlighting the need for further investigation into its pathogenesis.While the current literature has identified an association between gut microbiota dysregulation and cognitive deficits,the precise mechanisms involved remain insufficiently understood.This study hypothesizes that exosomelike(Exos-like)nanoparticles derived from the gut microbiota contribute to POCD by modulating autophagy-dependent ferroptosis in hippocampal neurons.In a rat model of CRC,significant alterations in the gut microbiota composition,including reduced microbial diversity and changes in the abundance of key taxa,are observed.Exosomes derived from these microbiota enhance neuronal uptake and trigger markers of ferroptosis,as evidenced by increased expressions of ATG5 and COX2,along with decreased levels of GPX4 and FTH1.These findings establish a mechanistic link between microbial dysbiosis,ferroptosis,and cognitive decline in POCD,providing new insights into potential therapeutic targets for CRC-associated POCD.
Ying Gao;Biao Xi;Yang Zhang;Mei Mei;Ming Zhai;Yunzhi Ling;Weiwei Chu
Department of Anesthesiology,the First Affiliated Hospital of Bengbu Medical University,Bengbu 233004,ChinaDepartment of Anesthesiology,the First Affiliated Hospital of Bengbu Medical University,Bengbu 233004,ChinaDepartment of Anesthesiology,the First Affiliated Hospital of Bengbu Medical University,Bengbu 233004,China Department of Anesthesiology,the First Affiliated Hospital of Soochow University,Suzhou 215006,ChinaDepartment of Anesthesiology,the First Affiliated Hospital of Bengbu Medical University,Bengbu 233004,ChinaDepartment of Anesthesiology,the First Affiliated Hospital of Bengbu Medical University,Bengbu 233004,ChinaDepartment of Anesthesiology,the First Affiliated Hospital of Bengbu Medical University,Bengbu 233004,ChinaDepartment of Plastic Surgery,the First Affiliated Hospital of Bengbu Medical University,Bengbu 233004,China
医药卫生
POCDCRCgut microbiotaExos-like nanoparticleautophagy-dependent ferroptosishippocampal neuron
《Acta Biochimica et Biophysica Sinica》 2026 (6)
P.1313-1328,16
supported by the grants from the Natural Science Research Project of the Anhui Educational Committee(Nos.2024H051245 and 2023H051935)the Health Research Program of Anhui(Nos.AHWJ2023A30127 and AHWJ2023A20228)the Natural Science Foundation of Anhui Province(No.2408085MH236)the Natural Science Project of Bengbu Medical University(No.2023byzd054).
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