{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T21:24:39Z","timestamp":1783113879505,"version":"3.54.6"},"reference-count":66,"publisher":"Wiley","issue":"37","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2023B1515230008"],"award-info":[{"award-number":["2023B1515230008"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2024A1515011463"],"award-info":[{"award-number":["2024A1515011463"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["B2024065"],"award-info":[{"award-number":["B2024065"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006407","name":"Natural Science Foundation of Henan Province","doi-asserted-by":"publisher","award":["252300420095"],"award-info":[{"award-number":["252300420095"]}],"id":[{"id":"10.13039\/501100006407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82571622"],"award-info":[{"award-number":["82571622"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Acquired cognitive impairments occur in diverse neurological and psychiatric conditions, yet the mechanisms linking neural circuit activity to neurovascular function remain poorly understood. Using a mouse model of nicotine withdrawal (WD), we identified an activity\u2010dependent NEPAS\u2013pentraxin\u20103 (PTX3) axis in mPFC neurons that couples circuit hypoactivity to cognitive deficits. In this model, NEPAS expression is significantly upregulated in mPFC neurons, accompanied by reduced myelin formation. Neuronal activity in mPFC and PVA is suppressed and chemogenetic activation of the PVA\u2013mPFC neural circuit downregulates NEPAS. Elevated neuronal NEPAS suppresses the secretion of PTX3, thereby impairing angiogenesis. Conversely, knockdown of neuronal NEPAS restores PTX3 expression and angiogenesis, alleviates myelin formation deficits, and improves cognitive memory following nicotine WD. Notably, activation of the PVA\u2013mPFC neural circuit produces similar therapeutic effects. Human transcriptomic data reveal a consistently elevated HIF\u20103\u03b1 expression in ex\u2010smokers versus controls. Our findings demonstrate that the NEPAS\u2013PTX3 axis in mPFC neurons links neural circuit hypoactivity to neurovascular and myelin deficits, providing a mechanistic framework for acquired cognitive impairment. This pathway represents a potential target for neuromodulation\u2010based therapies in prefrontal circuit dysfunction associated cognitive disorders.<\/jats:p>","DOI":"10.1002\/advs.202521069","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T10:52:32Z","timestamp":1775559152000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["An Activity\u2010Dependent NEPAS\u2013PTX3 Axis Links Neurovascular and Myelin Deficits to Cognitive Impairment"],"prefix":"10.1002","volume":"13","author":[{"given":"Boya","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Neurosurgery The First Affiliated Hospital of Shantou University Medical College  Shantou Guangdong China"},{"name":"Pain and Related Diseases Research Laboratory Shantou University Medical College  Shantou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zifei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The First Affiliated Hospital of Shantou University Medical College  Shantou Guangdong China"},{"name":"Pain and Related Diseases Research Laboratory Shantou University Medical College  Shantou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingmei","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The First Affiliated Hospital of Shantou University Medical College  Shantou Guangdong China"},{"name":"Pain and Related Diseases Research Laboratory Shantou University Medical College  Shantou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiale","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The First Affiliated Hospital of Shantou University Medical College  Shantou Guangdong China"},{"name":"Pain and Related Diseases Research Laboratory Shantou University Medical College  Shantou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiale","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The First Affiliated Hospital of Shantou University Medical College  Shantou Guangdong China"},{"name":"Pain and Related Diseases Research Laboratory Shantou University Medical College  Shantou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaochun","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The First Affiliated Hospital of Shantou University Medical College  Shantou Guangdong China"},{"name":"Pain and Related Diseases Research Laboratory Shantou University Medical College  Shantou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenfei","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Shantou University Medical College  Shantou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongsi","family":"Wang","sequence":"additional","affiliation":[{"name":"Beijing SeqWisdom Biotechnology Co., Ltd.  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The First Affiliated Hospital of Shantou University Medical College  Shantou Guangdong China"},{"name":"Pain and Related Diseases Research Laboratory Shantou University Medical College  Shantou Guangdong China"},{"name":"Department of Pharmacology Shantou University Medical College  Shantou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The First Affiliated Hospital of Shantou University Medical College  Shantou Guangdong China"},{"name":"Pain and Related Diseases Research Laboratory Shantou University Medical College  Shantou Guangdong China"},{"name":"Department of Pharmacology Shantou University Medical College  Shantou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peipei","family":"Liu","sequence":"additional","affiliation":[{"name":"Clinical Systems Biology Laboratories The First Affiliated Hospital of Zhengzhou University  Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5138-1446","authenticated-orcid":false,"given":"Bing","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The First Affiliated Hospital of Shantou University Medical College  Shantou Guangdong China"},{"name":"Pain and Related Diseases Research Laboratory Shantou University Medical College  Shantou Guangdong China"},{"name":"Department of Pharmacology Shantou University Medical College  Shantou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,7]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.2196\/jmir.2275"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2004.10.022"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213\u2010007\u20100797\u20109"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/14622200701188919"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3660\u201011.2012"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2023.110901"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.07.030"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2018.3"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.111.246116"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213\u2010025\u201006874\u2010z"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.182279"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0012\u20101606(03)00356\u20107"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2024.03.011"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593\u2010023\u201001515\u20100"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2015.3689"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M208681200"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/35107085"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.05\u20103788com"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01332\u201007"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004589"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26020649"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.12.002"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1028\u201022.2023"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2024.11.053"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aat2512"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2015.10.029"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2024.105989"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1041\u201010.2010"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000001497"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010017\u201000891\u2010z"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2011.06.025"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109\u2010018\u20101698\u20106"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018\u2010019\u201003387\u20109"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974\u2010014\u20100227\u2010y"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u20102012\u2010120067"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cccb.2021.100030"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201023337\u2010z"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.14521"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2010.08.008"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1428907"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593\u2010019\u20100582\u20101"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.07.017"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.04.052"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1944\u201011.2011"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/jemt.10249"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.22111"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010191293"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aao2861"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3849"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.07.051"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12821"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201010219\u20108"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/85138"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1220558110"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2018.02.018"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1177\/1947601911423654"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010020\u20100227\u2010y"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.04.019"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI9369"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI60842"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1179\/016164109X12445616596562"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010020\u201075838\u20104"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401\u2010023\u201001061\u20102"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23963"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2014.01.022"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X231167753"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202521069","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202521069","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202521069","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T21:09:29Z","timestamp":1783112969000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202521069"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,7]]},"references-count":66,"journal-issue":{"issue":"37","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/advs.202521069"],"URL":"https:\/\/doi.org\/10.1002\/advs.202521069","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,7]]},"assertion":[{"value":"2025-10-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e21069"}}