{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T17:29:16Z","timestamp":1775064556129,"version":"3.50.1"},"reference-count":44,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T00:00:00Z","timestamp":1765238400000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82474633"],"award-info":[{"award-number":["82474633"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Electroacupuncture (EA) has been widely used in Alzheimer's disease (AD) treatment. However, its underlying mechanisms remain poorly elucidated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>This study aimed to investigate the effects of EA on AD\u2010like phenotypes and explore the mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We first evaluated AD\u2010like behaviors and cerebral blood flow (CBF) changes in APP\n                      <jats:sub>swe<\/jats:sub>\n                      \/PS1dE9 (APP\/PS1) mice at different ages. Subsequently, the therapeutic effects of EA at acupoints\n                      <jats:italic>Baihui<\/jats:italic>\n                      (GV20),\n                      <jats:italic>Guanyuan<\/jats:italic>\n                      (CV4), and\n                      <jats:italic>Zusanli<\/jats:italic>\n                      (ST36), as well as sunitinib, a PDGFR\u03b2\u2010specific inhibitor, on AD\u2010like phenotypes in APP\/PS1 mice were investigated. CBF was monitored by laser speckle imaging, and hippocampal synaptic ultrastructure and microvascular morphology were examined by transmission electron microscopy (TEM). Western blot was performed to measure related protein expression. Finally, functional ultrasound (fUS) imaging was used to assess changes in brain\u2010wide functional connectivity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared with age\u2010matched wild\u2010type (WT) mice, 6\u2010 and 9\u2010month\u2010old APP\/PS1 mice exhibited significant cognitive decline, while all age groups (3\u2010, 6\u2010, and 9\u2010month\u2010old) of APP\/PS1 mice showed significantly reduced CBF. APP\/PS1 mice showed elevated expression of microvascular markers in both the hippocampus and cortex. EA significantly ameliorated AD\u2010like behaviors and prevented CBF reduction as well as microvascular deformation in 6\u2010month\u2010old APP\/PS1 mice compared with non\u2010treatment group. TEM and western blot analysis revealed damaged synaptic structure and reduced synaptic proteins in APP\/PS1 mice, all of which were markedly alleviated by EA treatment. In addition, EA treatment downregulated the aberrantly elevated expression of PDGFR\u03b2 and CD31, enhanced the levels of tight junction proteins (Occludin, Claudin\u20105, and ZO\u20101) and glucose transporter 1 (GLUT1), and suppressed the expression of inflammatory proteins. Of note, intervention with sunitinib also improved AD\u2010like behaviors in APP\/PS1 mice. Remarkably, fUS imaging results showed that EA enhanced the functional connection between hippocampal regions of APP\/PS1 mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our data demonstrates that EA ameliorates AD\u2010like phenotypes, potentially through preventing microangiopathy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.70696","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T07:01:57Z","timestamp":1765350117000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Electroacupuncture Prevents Against AD\u2010Like Phenotypes in APP\/PS1 Mice: Investigation of the Mechanisms From Cerebral Microangiopathy"],"prefix":"10.1002","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-1802-6166","authenticated-orcid":false,"given":"Chen","family":"Yang","sequence":"first","affiliation":[{"name":"Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine of IHM, and Key Laboratory of Molecular Biology (Brain Diseases) Anhui University of Chinese Medicine  Hefei China"},{"name":"Key Laboratory of Xin'an Medicine The Ministry of Education  Hefei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baobao","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine of IHM, and Key Laboratory of Molecular Biology (Brain Diseases) Anhui University of Chinese Medicine  Hefei China"},{"name":"Key Laboratory of Xin'an Medicine The Ministry of Education  Hefei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6767-1101","authenticated-orcid":false,"given":"Shaojie","family":"Yang","sequence":"additional","affiliation":[{"name":"Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine of IHM, and Key Laboratory of Molecular Biology (Brain Diseases) Anhui University of Chinese Medicine  Hefei China"},{"name":"The Second Affiliated Hospital of Anhui University of Chinese Medicine  Hefei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuncui","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine of IHM, and Key Laboratory of Molecular Biology (Brain Diseases) Anhui University of Chinese Medicine  Hefei China"},{"name":"Key Laboratory of Xin'an Medicine The Ministry of Education  Hefei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7432-6079","authenticated-orcid":false,"given":"Guoqi","family":"Zhu","sequence":"additional","affiliation":[{"name":"Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine of IHM, and Key Laboratory of Molecular Biology (Brain Diseases) Anhui University of Chinese Medicine  Hefei China"},{"name":"Key Laboratory of Xin'an Medicine The Ministry of Education  Hefei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingji","family":"wang","sequence":"additional","affiliation":[{"name":"Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine of IHM, and Key Laboratory of Molecular Biology (Brain Diseases) Anhui University of Chinese Medicine  Hefei China"},{"name":"The Second Affiliated Hospital of Anhui University of Chinese Medicine  Hefei China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12,9]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13016"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2023.10.008"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2024.109778"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202403980"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.066929"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-020-02215-w"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X20982383"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aav9518"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2025.03.002"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/1067541"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.14743"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ibneur.2025.03.001"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yhbeh.2012.04.006"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.wjam.2024.12.007"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2024.155639"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/HM9.0000000000000164"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-025-03266-x"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1162\/imag_a_00030"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2023.155009"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.10.008"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2024.115116"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04369-3"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-021-00357-7"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-021-00904-7"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.14059"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13821"},{"key":"e_1_2_14_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12906-017-2064-x"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2024.1346858"},{"key":"e_1_2_14_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2021.107844"},{"key":"e_1_2_14_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-021-02345-9"},{"key":"e_1_2_14_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22399-3"},{"key":"e_1_2_14_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.092170"},{"key":"e_1_2_14_34_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad8373"},{"key":"e_1_2_14_35_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X241304893"},{"key":"e_1_2_14_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2021.723953"},{"key":"e_1_2_14_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.01.003"},{"key":"e_1_2_14_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.14688"},{"key":"e_1_2_14_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-016-0454-x"},{"key":"e_1_2_14_40_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/6080282"},{"key":"e_1_2_14_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-05788-0"},{"key":"e_1_2_14_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01456-w"},{"key":"e_1_2_14_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2021.661838"},{"key":"e_1_2_14_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00421"},{"key":"e_1_2_14_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.105322"}],"container-title":["CNS Neuroscience &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cns.70696","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T09:21:01Z","timestamp":1767086461000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cns.70696"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":44,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/cns.70696"],"URL":"https:\/\/doi.org\/10.1002\/cns.70696","archive":["Portico"],"relation":{},"ISSN":["1755-5930","1755-5949"],"issn-type":[{"value":"1755-5930","type":"print"},{"value":"1755-5949","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"2025-07-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70696"}}