{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:29:22Z","timestamp":1792182562856,"version":"4.4.0"},"reference-count":47,"publisher":"SAGE Publications","issue":"7-9","license":[{"start":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:00:00Z","timestamp":1767916800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81873423"],"award-info":[{"award-number":["81873423"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82200101"],"award-info":[{"award-number":["82200101"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2026,3,1]]},"abstract":"<jats:sec>\n                    <jats:title>Aims:<\/jats:title>\n                    <jats:p>Mitochondrial homeostasis is essential for maintaining central nervous system function. Both inflammation and oxidative stress induced by chronic intermittent hypoxia (CIH) can result in neuronal mitochondrial injury in obstructive sleep apnea syndrome (OSAS)-related cognitive dysfunction. Recent evidence implicates neuronal impairment caused by abnormal activation of microglia as a key contributor to CIH-induced cognitive dysfunction. However, the mechanism between microglia and neuronal injury remains elusive. This study seeks to elucidate the underlying mechanism of microglia-mediated neuronal injury in CIH-induced cognitive dysfunction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Both the levels of pro-inflammatory factors and reactive oxygen species (ROS) were elevated; neuronal mitochondrial and cytomembrane injury and neuronal pyroptosis also occurred in CIH models\n                      <jats:italic toggle=\"yes\">in vitro and in\u00a0vivo<\/jats:italic>\n                      . Microglial cells RNA sequencing data revealed that CIH upregulated the nucleotide-binding and oligomerization domain\u2013like receptor pathway, and\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      experiments confirmed that the thioredoxin-interacting protein (TXNIP)\/nucleotide-binding and oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3)\/gasdermin D (GSDMD) pathway modulated inflammation and oxidative stress in BV-2 cells and regulated neuronal mitochondrial and cytomembrane injury and pyroptosis. Co-immunoprecipitation results verified that TXNIP bound directly to NLRP3 in BV-2 cells. Furthermore, GSDMD-derived inhibitor (Ac-FLTD-CMK) abolished the elevation in inflammation and oxidative stress markers induced by\n                      <jats:italic toggle=\"yes\">TXNIP<\/jats:italic>\n                      overexpression after CIH exposure. In addition, it alleviated HT-22 cells\u2019 mitochondrial and cytomembrane injury\u00a0and suppressed the activation of TXNIP\/NLRP3\/GSDMD pathway in BV-2 cells induced by CIH after the application of mitochondrial antioxidant Mito-TEMPO to BV-2 cells, thereby mitigating microglia-mediated neuronal pyroptosis. These findings were corroborated by\n                      <jats:italic toggle=\"yes\">in\u00a0vivo<\/jats:italic>\n                      experiments.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Innovation and Conclusion:<\/jats:title>\n                    <jats:p>\n                      These results reveal that microglial TXNIP\/NLRP3\/GSDMD pathway activation is a key mechanism linking CIH to neuronal injury in OSAS-related cognitive dysfunction. Inhibition of TXNIP\/NLRP3\/GSDMD pathway and antioxidant therapy could protect against CIH-induced cognitive dysfunction by ameliorating the damaging effects of cytokines of inflammation and oxidative stress from microglia, while preventing neuronal mitochondrial and cytomembrane injury and pyroptosis. This work identifies a promising target for pharmacological intervention in OSAS-related cognitive dysfunction.\n                      <jats:italic toggle=\"yes\">Antioxid. Redox Signal.<\/jats:italic>\n                      44, 373\u2013392.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/15230864251406615","type":"journal-article","created":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T04:06:47Z","timestamp":1768018007000},"page":"373-392","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Inhibition of TXNIP\/NLRP3\/GSDMD Pathway and Antioxidant Therapy Mitigate Cognitive Dysfunction Induced by Chronic Intermittent Hypoxia"],"prefix":"10.1177","volume":"44","author":[{"given":"Hongwei","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine and Sleep Lab, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Biomedical and Health Sciences, Anhui University of Science and Technology, Chuzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiwen","family":"Ou","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine and Sleep Lab, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine and Sleep Lab, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 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