{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T03:38:55Z","timestamp":1792553935227,"version":"4.5.0"},"reference-count":12,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T00:00:00Z","timestamp":1784937600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"vor","delay-in-days":88,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2025-00562132"],"award-info":[{"award-number":["RS-2025-00562132"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008783","name":"National Research Council of Science and Technology","doi-asserted-by":"publisher","award":["GTL25071-000"],"award-info":[{"award-number":["GTL25071-000"]}],"id":[{"id":"10.13039\/501100008783","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Brain"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Vascular cognitive impairment (VCI) is a major cause of dementia with limited treatment options. Transcutaneous auricular vagus nerve stimulation (taVNS) is a noninvasive neuromodulation approach that has shown cognitive benefits, but its molecular basis remains unclear. Here, we employed a mouse model of transient bilateral common carotid artery occlusion (tBCCAO) to identify molecular candidates underlying the cognitive restorative effects of taVNS. tBCCAO impaired cognitive function as revealed by behavioral assessments, whereas taVNS restored behavioral performance. Hippocampal proteomic analysis identified 58 proteins altered in tBCCAO compared with sham, and 16 proteins significantly modulated by taVNS compared with tBCCAO. Among these, a core set of taVNS-responsive proteins exhibited a normalization-like pattern, suggesting that taVNS shifted ischemia-associated proteomic alterations toward a near-normal state rather than simply amplifying or suppressing the overall response. These findings suggest that taVNS may improve VCI by restoring hippocampal protein dysregulation following transient cerebral hypoperfusion and highlight molecular targets as candidate mechanisms for further investigation.<\/jats:p>","DOI":"10.1186\/s13041-026-01339-6","type":"journal-article","created":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T14:45:33Z","timestamp":1784990733000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Proteomic analysis of transcutaneous auricular vagus nerve stimulation induced cognitive restoration in a mouse model of vascular cognitive impairment"],"prefix":"10.1186","volume":"19","author":[{"given":"Seunghwan","family":"Choi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Hyun","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chan Su","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun Kwang","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,25]]},"reference":[{"issue":"4","key":"1339_CR1","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1161\/STROKEAHA.123.044174","volume":"55","author":"BYM Ip","year":"2024","unstructured":"Ip BYM, Ko H, Lam BYK, Au LWC, Lau AYL, Huang J, et al. Current and future treatments of vascular cognitive impairment. Stroke. 2024;55(4):822\u201339.","journal-title":"Stroke"},{"issue":"8","key":"1339_CR2","doi-asserted-by":"publisher","first-page":"1542","DOI":"10.1161\/ATVBAHA.119.311908","volume":"39","author":"FJ Wolters","year":"2019","unstructured":"Wolters FJ, Ikram MA. Epidemiology of vascular dementia. Arterioscler Thromb Vasc Biol. 2019;39(8):1542\u20139.","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"1339_CR3","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-026-02331-3","author":"MJ Lennon","year":"2026","unstructured":"Lennon MJ, Sachdev PS. Vascular cognitive impairment and dementia: prevention, treatments, mechanisms and management options for the future. Neuropsychopharmacology. 2026. https:\/\/doi.org\/10.1038\/s41386-026-02331-3.","journal-title":"Neuropsychopharmacology"},{"issue":"3","key":"1339_CR4","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1111\/ner.12541","volume":"20","author":"N Yakunina","year":"2017","unstructured":"Yakunina N, Kim SS, Nam E-C. Optimization of transcutaneous vagus nerve stimulation using functional MRI. Neuromodulation. 2017;20(3):290\u2013300.","journal-title":"Neuromodulation"},{"issue":"19","key":"1339_CR5","doi-asserted-by":"publisher","DOI":"10.3390\/cells11193019","volume":"11","author":"S Choi","year":"2022","unstructured":"Choi S, Jang DC, Chung G, Kim SK. Transcutaneous auricular vagus nerve stimulation enhances cerebrospinal fluid circulation and restores cognitive function in the rodent model of vascular cognitive impairment. Cells. 2022;11(19):3019.","journal-title":"Cells"},{"issue":"6","key":"1339_CR6","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1016\/j.brs.2022.09.003","volume":"15","author":"L Wang","year":"2022","unstructured":"Wang L, Zhang J, Guo C, He J, Zhang S, Wang Y, et al. The efficacy and safety of transcutaneous auricular vagus nerve stimulation in patients with mild cognitive impairment: a double blinded randomized clinical trial. Brain Stimul. 2022;15(6):1405\u201314.","journal-title":"Brain Stimul"},{"issue":"1","key":"1339_CR7","doi-asserted-by":"publisher","first-page":"109","DOI":"10.4196\/kjpp.24.266","volume":"29","author":"S Choi","year":"2025","unstructured":"Choi S, Baek IS, Lee K, Kim SK. Low-frequency auricular vagus nerve stimulation facilitates cerebrospinal fluid influx by promoting vasomotion. Korean J Physiol Pharmacol. 2025;29(1):109\u201316.","journal-title":"Korean J Physiol Pharmacol"},{"issue":"2","key":"1339_CR8","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1016\/j.brs.2019.12.024","volume":"13","author":"A V\u00e1zquez-Oliver","year":"2020","unstructured":"V\u00e1zquez-Oliver A, Brambilla-Pisoni C, Domingo-Gainza M, Maldonado R, Ivorra A, Ozaita A. Auricular transcutaneous vagus nerve stimulation improves memory persistence in na\u00efve mice and in an intellectual disability mouse model. Brain Stimul. 2020;13(2):494\u20138.","journal-title":"Brain Stimul"},{"issue":"12","key":"1339_CR9","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1038\/nrn2738","volume":"10","author":"L Minichiello","year":"2009","unstructured":"Minichiello L. TrkB signalling pathways in LTP and learning. Nat Rev Neurosci. 2009;10(12):850\u201360.","journal-title":"Nat Rev Neurosci"},{"key":"1339_CR10","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2019.112080","volume":"373","author":"AQ Farrand","year":"2019","unstructured":"Farrand AQ, Helke KL, Aponte-Cofres\u00ed L, Gooz MB, Gregory RA, Hinson VK, et al. Effects of vagus nerve stimulation are mediated in part by TrkB in a Parkinson\u2019s disease model. Behav Brain Res. 2019;373:112080.","journal-title":"Behav Brain Res"},{"key":"1339_CR11","doi-asserted-by":"crossref","unstructured":"Driskill CM, Childs JE, Phensy AJ, Rodriguez SR, O\u2019Brien JT, Lindquist KL, et al. Vagus nerve stimulation (VNS) modulates synaptic plasticity in the infralimbic cortex via Trk-B receptor activation to reduce drug-seeking in male rats. The Journal of Neuroscience. 2024:e0107242024.","DOI":"10.1101\/2024.01.25.577293"},{"issue":"5","key":"1339_CR12","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0034844","volume":"7","author":"H Furmaga","year":"2012","unstructured":"Furmaga H, Carreno FR, Frazer A. Vagal nerve stimulation rapidly activates brain-derived neurotrophic factor receptor TrkB in rat brain. PLoS ONE. 2012;7(5):e34844.","journal-title":"PLoS ONE"}],"container-title":["Molecular Brain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13041-026-01339-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13041-026-01339-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13041-026-01339-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T02:50:03Z","timestamp":1792551003000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13041-026-01339-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,25]]},"references-count":12,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1339"],"URL":"https:\/\/doi.org\/10.1186\/s13041-026-01339-6","relation":{},"ISSN":["1756-6606"],"issn-type":[{"value":"1756-6606","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,25]]},"assertion":[{"value":"15 May 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The animal experiments followed protocols approved by the Animal Care and Use Committee of Kyung Hee University (KHSASP-26\u2013287).","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"A company (Neurogrin Inc.) founded by S.K.K. holds the patent application related to the contents of this article (10\u20132023-0168520 in Korea). The remaining authors declare no competing Interests.","order":3,"name":"Ethics","label":"Competing Interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"75"}}