{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T05:52:08Z","timestamp":1778910728233,"version":"3.51.4"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":27,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"Zunyi Medical University\u2019s \u201c12345\u201d Future Talent Training Program \"Future Clinical Famous Doctors\" Project","award":["20211004"],"award-info":[{"award-number":["20211004"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-34689-7","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T03:46:59Z","timestamp":1770954419000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Activation of M1mAChR\u2019s improves spatial learning and memory deficits in rats exposed to chronic intermittent hypoxia"],"prefix":"10.1038","volume":"16","author":[{"given":"Qin","family":"Huang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ci","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haijun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunfei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaodong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zucai","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,2,13]]},"reference":[{"issue":"9918","key":"34689_CR1","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1016\/S0140-6736(13)60734-5","volume":"383","author":"AS Jordan","year":"2014","unstructured":"Jordan, A. S., McSharry, D. G. & Malhotra, A. Adult obstructive sleep apnoea. Lancet 383 (9918), 736\u2013747 (2014).","journal-title":"Lancet"},{"key":"34689_CR2","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.smrv.2017.03.005","volume":"38","author":"M Olaithe","year":"2018","unstructured":"Olaithe, M., Bucks, R. S., Hillman, D. R. & Eastwood, P. R. Cognitive deficits in obstructive sleep apnea: Insights from a meta-review and comparison with deficits observed in COPD, insomnia, and sleep deprivation. Sleep. Med. Rev. 38, 39\u201349 (2018).","journal-title":"Sleep. Med. Rev."},{"issue":"5","key":"34689_CR3","doi-asserted-by":"publisher","first-page":"1209","DOI":"10.1016\/j.chest.2024.05.028","volume":"166","author":"A Azarbarzin","year":"2024","unstructured":"Azarbarzin, A., Labarca, G., Kwon, Y. & Wellman, A. Physiologic consequences of upper airway obstruction in sleep apnea. Chest 166 (5), 1209\u20131217 (2024).","journal-title":"Chest"},{"issue":"1","key":"34689_CR4","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1186\/s12974-020-01905-2","volume":"17","author":"X Liu","year":"2020","unstructured":"Liu, X. et al. The relationship between inflammation and neurocognitive dysfunction in obstructive sleep apnea syndrome. J. Neuroinflammation. 17 (1), 229 (2020).","journal-title":"J. Neuroinflammation"},{"issue":"8","key":"34689_CR5","doi-asserted-by":"publisher","first-page":"5083","DOI":"10.1007\/s12035-023-03899-3","volume":"61","author":"X Zhang","year":"2024","unstructured":"Zhang, X., Zhou, H., Liu, H. & Xu, P. Role of oxidative stress in the occurrence and development of cognitive dysfunction in patients with obstructive sleep apnea syndrome. Mol. Neurobiol. 61 (8), 5083\u20135101 (2024).","journal-title":"Mol. Neurobiol."},{"issue":"3","key":"34689_CR6","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.1007\/s11325-024-03001-8","volume":"28","author":"Y He","year":"2024","unstructured":"He, Y. et al. Obstructive sleep apnea affects cognition: Dual effects of intermittent hypoxia on neurons. Sleep. Breath. 28 (3), 1051\u20131065 (2024).","journal-title":"Sleep. Breath."},{"issue":"4","key":"34689_CR7","first-page":"1071","volume":"22","author":"ZW Wen","year":"2018","unstructured":"Wen, Z. W., Liang, D. S., Cai, X. H. & Chen, J. The role of AMPK\/mTOR signal pathway in brain injury following chronic intermittent hypoxia in growing rats. Eur. Rev. Med. Pharmacol. Sci. 22 (4), 1071\u20131077 (2018).","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"issue":"8","key":"34689_CR8","doi-asserted-by":"publisher","first-page":"e746","DOI":"10.1038\/cddis.2013.242","volume":"4","author":"G Wang","year":"2013","unstructured":"Wang, G. et al. The JAK2\/STAT3 and mitochondrial pathways are essential for quercetin nanoliposome-induced C6 glioma cell death. Cell. Death Dis. 4 (8), e746 (2013).","journal-title":"Cell. Death Dis."},{"issue":"6","key":"34689_CR9","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1177\/15353702211062509","volume":"247","author":"T Jia","year":"2022","unstructured":"Jia, T., Xing, Z. & Wang, Li, G. Protective effect of dexmedetomidine on intestinal mucosal barrier function in rats after cardiopulmonary bypass. Exp. Biol. Med. (Maywood). 247 (6), 498\u2013508 (2022).","journal-title":"Exp. Biol. Med. (Maywood)"},{"issue":"1","key":"34689_CR10","doi-asserted-by":"publisher","first-page":"1872","DOI":"10.1080\/21655979.2021.2018976","volume":"13","author":"P Sun","year":"2022","unstructured":"Sun, P. & Xue, Y. Silence of TANK-binding kinase 1 (TBK1) regulates extracellular matrix degradation of chondrocyte in osteoarthritis by janus kinase (JAK)-signal transducer of activators of transcription (STAT) signaling. Bioengineered 13 (1), 1872\u20131879 (2022).","journal-title":"Bioengineered"},{"issue":"21","key":"34689_CR11","doi-asserted-by":"publisher","first-page":"3857","DOI":"10.1016\/j.cell.2022.09.023","volume":"185","author":"RL Philips","year":"2022","unstructured":"Philips, R. L. et al. The JAK-STAT pathway at 30: Much learned, much more to do. Cell 185 (21), 3857\u20133876 (2022).","journal-title":"Cell"},{"issue":"6","key":"34689_CR12","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1016\/j.neuron.2016.09.006","volume":"91","author":"EC Ballinger","year":"2016","unstructured":"Ballinger, E. C., Ananth, M., Talmage, D. A. & Role, L. W. Basal forebrain cholinergic circuits and signaling in cognition and cognitive decline. Neuron 91 (6), 1199\u20131218 (2016).","journal-title":"Neuron"},{"issue":"6","key":"34689_CR13","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1021\/acschemneuro.6b00278","volume":"8","author":"EP Lebois","year":"2017","unstructured":"Lebois, E. P. et al. Disease-modifying effects of M(1) muscarinic acetylcholine receptor activation in an alzheimer\u2019s disease mouse model. ACS Chem. Neurosci. 8 (6), 1177\u20131187 (2017).","journal-title":"ACS Chem. Neurosci."},{"issue":"9","key":"34689_CR14","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1176\/appi.ajp.2020.20081212","volume":"178","author":"YB Joshi","year":"2021","unstructured":"Joshi, Y. B. et al. Anticholinergic medication burden-associated cognitive impairment in schizophrenia. Am. J. Psychiatry. 178 (9), 838\u2013847 (2021).","journal-title":"Am. J. Psychiatry"},{"key":"34689_CR15","doi-asserted-by":"publisher","first-page":"869","DOI":"10.3389\/fphys.2019.00869","volume":"10","author":"A Sto\u017eer","year":"2019","unstructured":"Sto\u017eer, A. et al. Heterogeneity and delayed activation as hallmarks of self-organization and criticality in excitable tissue. Front. Physiol. 10, 869 (2019).","journal-title":"Front. Physiol."},{"issue":"2","key":"34689_CR16","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1016\/j.neuron.2011.11.024","volume":"73","author":"CS Nicolas","year":"2012","unstructured":"Nicolas, C. S. et al. The Jak\/STAT pathway is involved in synaptic plasticity. Neuron 73 (2), 374\u2013390 (2012).","journal-title":"Neuron"},{"issue":"2","key":"34689_CR17","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1038\/mp.2008.105","volume":"14","author":"T Chiba","year":"2009","unstructured":"Chiba, T. et al. Amyloid-beta causes memory impairment by disturbing the JAK2\/STAT3 axis in hippocampal neurons. Mol. Psychiatry. 14 (2), 206\u2013222 (2009).","journal-title":"Mol. Psychiatry"},{"key":"34689_CR18","doi-asserted-by":"crossref","unstructured":"Qin Huang, P. et al. Inhibition of ERK1\/2 regulates cognitive function by decreasing expression levels of PSD-95 in the hippocampus of CIH rats. (2022).","DOI":"10.1111\/EJN.15635\/v2\/response1"},{"issue":"6","key":"34689_CR19","doi-asserted-by":"publisher","first-page":"1471","DOI":"10.1111\/ejn.15635","volume":"55","author":"Q Huang","year":"2022","unstructured":"Huang, Q. et al. Inhibition of ERK1\/2 regulates cognitive function by decreasing expression levels of PSD-95 in the hippocampus of CIH rats. Eur. J. Neurosci. 55 (6), 1471\u20131482 (2022).","journal-title":"Eur. J. Neurosci."},{"issue":"9","key":"34689_CR20","doi-asserted-by":"publisher","first-page":"878","DOI":"10.1161\/CIRCULATIONAHA.120.048202","volume":"143","author":"CE Verrall","year":"2021","unstructured":"Verrall, C. E. et al. Neurocognitive dysfunction and smaller brain volumes in adolescents and adults with a Fontan circulation. Circulation 143 (9), 878\u2013891 (2021).","journal-title":"Circulation"},{"key":"34689_CR21","doi-asserted-by":"crossref","unstructured":"Cerium oxide nanoparticles promote neurogenesis and abrogate hypoxia-induced memory. Impairment through AMPK-PKC-CBP signaling cascade [retraction]. Int. J. Nanomed. 17, 5163\u20135164 (2022).","DOI":"10.2147\/IJN.S395863"},{"issue":"5868","key":"34689_CR22","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1038\/297681a0","volume":"297","author":"RG Morris","year":"1982","unstructured":"Morris, R. G., Garrud, P., Rawlins, J. N. & O\u2019Keefe, J. Place navigation impaired in rats with hippocampal lesions. Nature 297 (5868), 681\u2013683 (1982).","journal-title":"Nature"},{"key":"34689_CR23","doi-asserted-by":"publisher","first-page":"119747","DOI":"10.1016\/j.lfs.2021.119747","volume":"284","author":"YJ Tan","year":"2021","unstructured":"Tan, Y. J., Lee, Y. T., Mancera, R. L. & Oon, C. E. BZD9L1 sirtuin inhibitor: Identification of key molecular targets and their biological functions in HCT 116 colorectal cancer cells. Life Sci. 284, 119747 (2021).","journal-title":"Life Sci."},{"key":"34689_CR24","doi-asserted-by":"publisher","first-page":"36949","DOI":"10.1038\/srep36949","volume":"6","author":"C Li","year":"2016","unstructured":"Li, C. et al. Qishen granules inhibit myocardial inflammation injury through regulating arachidonic acid metabolism. Sci. Rep. 6, 36949 (2016).","journal-title":"Sci. Rep."},{"issue":"3","key":"34689_CR25","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1038\/cdd.2011.122","volume":"19","author":"MM Caffarel","year":"2012","unstructured":"Caffarel, M. M. et al. Constitutive activation of JAK2 in mammary epithelium elevates Stat5 signalling, promotes alveologenesis and resistance to cell death, and contributes to tumourigenesis. Cell. Death Differ. 19 (3), 511\u2013522 (2012).","journal-title":"Cell. Death Differ."},{"issue":"7","key":"34689_CR26","doi-asserted-by":"publisher","first-page":"2050","DOI":"10.7150\/jca.65875","volume":"13","author":"D Xu","year":"2022","unstructured":"Xu, D., Shen, H., Tian, M., Chen, W. & Zhang, X. Cucurbitacin I inhibits the proliferation of pancreatic cancer through the JAK2\/STAT3 signalling pathway in vivo and in vitro. J. Cancer. 13 (7), 2050\u20132060 (2022).","journal-title":"J. Cancer"},{"issue":"1","key":"34689_CR27","doi-asserted-by":"publisher","first-page":"4115","DOI":"10.1038\/s41467-020-17920-z","volume":"11","author":"G La Sala","year":"2020","unstructured":"La Sala, G. et al. Selective Inhibition of STAT3 signaling using monobodies targeting the coiled-coil and N-terminal domains. Nat. Commun. 11 (1), 4115 (2020).","journal-title":"Nat. Commun."},{"issue":"1","key":"34689_CR28","doi-asserted-by":"publisher","first-page":"8849","DOI":"10.1038\/s41598-019-45150-x","volume":"9","author":"R Bischof","year":"2019","unstructured":"Bischof, R., Gjevestad, J. G. O., Ordiz, A., Eldegard, K. & Milleret, C. High frequency GPS bursts and path-level analysis reveal linear feature tracking by red foxes. Sci. Rep. 9 (1), 8849 (2019).","journal-title":"Sci. Rep."},{"issue":"11","key":"34689_CR29","doi-asserted-by":"publisher","first-page":"1475","DOI":"10.1182\/blood-2016-02-698027","volume":"128","author":"Y Mao","year":"2016","unstructured":"Mao, Y. et al. IL-15 activates mTOR and primes stress-activated gene expression leading to prolonged antitumor capacity of NK cells. Blood 128 (11), 1475\u20131489 (2016).","journal-title":"Blood"},{"issue":"7","key":"34689_CR30","doi-asserted-by":"publisher","first-page":"2263","DOI":"10.7150\/thno.83340","volume":"13","author":"M Wang","year":"2023","unstructured":"Wang, M. et al. OTUD1 promotes pathological cardiac remodeling and heart failure by targeting STAT3 in cardiomyocytes. Theranostics 13 (7), 2263\u20132280 (2023).","journal-title":"Theranostics"},{"issue":"3","key":"34689_CR31","doi-asserted-by":"publisher","first-page":"597","DOI":"10.5114\/aoms.2016.63261","volume":"14","author":"HM Qu","year":"2018","unstructured":"Qu, H. M., Qu, L. P., Li, X. Y. & Pan, X. Z. Overexpressed HO-1 is associated with reduced STAT3 activation in preeclampsia placenta and inhibits STAT3 phosphorylation in placental JEG-3 cells under hypoxia. Arch. Med. Sci. 14 (3), 597\u2013607 (2018).","journal-title":"Arch. Med. Sci."},{"key":"34689_CR32","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/j.neuroscience.2019.07.020","volume":"416","author":"H Zhao","year":"2019","unstructured":"Zhao, H. et al. Colivelin rescues ischemic neuron and axons involving JAK\/STAT3 signaling pathway. Neuroscience 416, 198\u2013206 (2019).","journal-title":"Neuroscience"},{"issue":"1","key":"34689_CR33","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1111\/epi.13965","volume":"59","author":"P Klein","year":"2018","unstructured":"Klein, P. et al. Commonalities in epileptogenic processes from different acute brain insults: Do they translate? Epilepsia 59 (1), 37\u201366 (2018).","journal-title":"Epilepsia"},{"issue":"2","key":"34689_CR34","first-page":"3146","volume":"17","author":"W Wang","year":"2018","unstructured":"Wang, W. & Hu, W. Salvianolic acid B recovers cognitive deficits and angiogenesis in a cerebral small vessel disease rat model via the STAT3\/VEGF signaling pathway. Mol. Med. Rep. 17 (2), 3146\u20133151 (2018).","journal-title":"Mol. Med. Rep."},{"key":"34689_CR35","doi-asserted-by":"publisher","first-page":"4163188","DOI":"10.1155\/2022\/4163188","volume":"2022","author":"ZA Zhang","year":"2022","unstructured":"Zhang, Z. A. et al. Insight into the effects of High-Altitude hypoxic exposure on learning and memory. Oxid. Med. Cell. Longev. 2022, 4163188 (2022).","journal-title":"Oxid. Med. Cell. Longev."},{"issue":"8","key":"34689_CR36","doi-asserted-by":"publisher","first-page":"1426","DOI":"10.1038\/npp.2013.39","volume":"38","author":"SJ Park","year":"2013","unstructured":"Park, S. J. et al. Inactivation of JAK2\/STAT3 signaling axis and downregulation of M1 mAChR cause cognitive impairment in Klotho mutant mice, a genetic model of aging. Neuropsychopharmacology 38 (8), 1426\u20131437 (2013).","journal-title":"Neuropsychopharmacology"},{"key":"34689_CR37","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.neuint.2018.03.009","volume":"116","author":"HN Mai","year":"2018","unstructured":"Mai, H. N. et al. Exposure to far-infrared rays attenuates methamphetamine-induced recognition memory impairment via modulation of the muscarinic M1 receptor, Nrf2, and PKC. Neurochem Int. 116, 63\u201376 (2018).","journal-title":"Neurochem Int."},{"issue":"8","key":"34689_CR38","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1002\/hipo.22961","volume":"28","author":"CR Galloway","year":"2018","unstructured":"Galloway, C. R. et al. Hippocampal place cell dysfunction and the effects of muscarinic M(1) receptor agonism in a rat model of alzheimer\u2019s disease. Hippocampus 28 (8), 568\u2013585 (2018).","journal-title":"Hippocampus"},{"key":"34689_CR39","doi-asserted-by":"publisher","first-page":"1340725","DOI":"10.3389\/fnmol.2023.1340725","volume":"16","author":"LM Mao","year":"2023","unstructured":"Mao, L. M., Young, L., Chu, X. P. & Wang, J. Q. Regulation of Src family kinases by muscarinic acetylcholine receptors in heterologous cells and neurons. Front. Mol. Neurosci. 16, 1340725 (2023).","journal-title":"Front. Mol. Neurosci."},{"issue":"3","key":"34689_CR40","doi-asserted-by":"publisher","first-page":"106133","DOI":"10.1016\/j.isci.2023.106133","volume":"26","author":"T Sumi","year":"2023","unstructured":"Sumi, T. & Harada, K. Muscarinic acetylcholine receptor-dependent and NMDA receptor-dependent LTP and LTD share the common AMPAR trafficking pathway. iScience 26 (3), 106133 (2023).","journal-title":"iScience"},{"key":"34689_CR41","doi-asserted-by":"crossref","unstructured":"Zent, K. H. & Dell\u2019Acqua, M. L. Synapse-to-nucleus ERK\u2192CREB transcriptional signaling requires dendrite-to-soma Ca(2+) propagation mediated by L-type voltage-gated Ca(2+) channels. J. Neurosci. ;45(4) (2025).","DOI":"10.1523\/JNEUROSCI.1216-24.2024"},{"key":"34689_CR42","doi-asserted-by":"publisher","first-page":"1421554","DOI":"10.3389\/fpsyt.2024.1421554","volume":"15","author":"SE Yohn","year":"2024","unstructured":"Yohn, S. E., Harvey, P. D., Brannan, S. K. & Horan, W. P. The potential of muscarinic M(1) and M(4) receptor activators for the treatment of cognitive impairment associated with schizophrenia. Front. Psychiatry. 15, 1421554 (2024).","journal-title":"Front. Psychiatry"},{"issue":"14","key":"34689_CR43","doi-asserted-by":"publisher","first-page":"2114","DOI":"10.1111\/bph.15982","volume":"181","author":"HTM Nguyen","year":"2024","unstructured":"Nguyen, H. T. M. et al. Opportunities and challenges for the development of M(1) muscarinic receptor positive allosteric modulators in the treatment for neurocognitive deficits. Br. J. Pharmacol. 181 (14), 2114\u20132142 (2024).","journal-title":"Br. J. Pharmacol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-34689-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-34689-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-34689-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T09:47:41Z","timestamp":1773308861000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-34689-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,13]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["34689"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-34689-7","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,13]]},"assertion":[{"value":"31 March 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"8836"}}