{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T03:41:39Z","timestamp":1779334899673,"version":"3.51.4"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T00:00:00Z","timestamp":1731974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2022M3A9B6017813"],"award-info":[{"award-number":["2022M3A9B6017813"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Immune dysfunction is a major cause of neuroinflammation and accelerates the progression of Parkinson\u2019s disease (PD). Numerous studies have shown that stimulation of specific acupuncture points (acupoints) can ameliorate PD symptoms. The purpose of this study was to investigate whether attaching microneedles to acupoints would improve PD pathology by recovering immune dysfunction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The PD mouse model was induced by intrastriatal injection of 6-hydroxydopamine (6-OHDA), and microneedle patches (MPs) or sham patches (SPs) were attached to GB20 and GB34, representative acupoints for treating PD for 14 days.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>First, the behavioral experiment showed that motor disorders induced by 6-OHDA were significantly improved by MP. Simultaneously, 6-OHDA-induced dopaminergic neuronal death and brain neuroinflammation decreased. Conversely, SP had no effect on behavioral disorders, neuronal death, or neuroinflammation. Measurement results from flow cytometry of immune cells in the brain and blood revealed a disruption in the CD4+\/CD8+ ratio in the 6-OHDA group, which was significantly restored in the MP group. The brain mRNA expression of cytokines was significantly increased in the 6-OHDA group, which was significantly decreased by MP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Overall, our results suggest that the attachment of MPs to GB20 and GB34 is a new method to effectively improve the pathology of PD by restoring peripheral and brain immune function.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1454102","type":"journal-article","created":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T05:10:28Z","timestamp":1731993028000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Stimulation of microneedles alleviates pathology of Parkinson\u2019s disease in mice by regulating the CD4+\/CD8+ cells from the periphery to the brain"],"prefix":"10.3389","volume":"15","author":[{"given":"Jin Hee","family":"Kim","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yujin","family":"Choi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin Se","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanbyeol","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"In Gyoung","family":"Ju","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Na Young","family":"Yoo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sookie","family":"La","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Do Hyeon","family":"Jeong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changsu","family":"Na","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hi-Joon","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myung Sook","family":"Oh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,11,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2022.12.016","article-title":"Gut-initiated neuroprotection in Parkinson's disease: When microbes turn the tables in the battle against neuroinflammation","volume":"108","author":"Barros-Santos","year":"2023","journal-title":"Brain Behav Immun"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.4062\/biomolther.2023.098","article-title":"6-shogaol, an active ingredient of ginger, improves intestinal and brain abnormalities in proteus mirabilis-induced parkinson's disease mouse model","volume":"31","author":"Huh","year":"2023","journal-title":"Biomol Ther (Seoul)"},{"key":"B3","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/S0140-6736(23)01478-2","article-title":"The pathogenesis of Parkinson's disease","volume":"403","author":"Morris","year":"2024","journal-title":"Lancet"},{"key":"B4","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1111\/ene.14108","article-title":"Parkinson disease","volume":"27","author":"Balestrino","year":"2020","journal-title":"Eur J Neurol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-022-00684-6","article-title":"Inflammation and immune dysfunction in Parkinson disease","volume":"22","author":"Tansey","year":"2022","journal-title":"Nat Rev Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2024.02.013","article-title":"Systemic inflammation and risk of Parkinson's disease: A prospective cohort study and genetic analysis","volume":"117","author":"Li","year":"2024","journal-title":"Brain Behav Immun"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.4062\/biomolther.2022.073","article-title":"Hycanthone inhibits inflammasome activation and neuroinflammation-induced depression-like behaviors in mice","volume":"31","author":"Boo","year":"2023","journal-title":"Biomol Ther (Seoul)"},{"key":"B8","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.bbi.2022.09.010","article-title":"Emerging roles of leptin in Parkinson's disease: Chronic inflammation, neuroprotection and more","volume":"107","author":"Regensburger","year":"2023","journal-title":"Brain Behav Immun"},{"key":"B9","doi-asserted-by":"publisher","first-page":"16766","DOI":"10.3390\/ijms242316766","article-title":"The role of immune dysfunction in parkinson's disease development","volume":"24","author":"Cossu","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3233\/JPD-223152","article-title":"T lymphocytes in parkinson's disease","volume":"12","author":"Contaldi","year":"2022","journal-title":"J Parkinsons Dis"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2023.07.005","article-title":"The systemic immune response in Parkinson's disease: focus on the peripheral immune component","volume":"46","author":"Lauritsen","year":"2023","journal-title":"Trends Neurosci"},{"key":"B12","doi-asserted-by":"publisher","first-page":"8421","DOI":"10.3390\/ijms21228421","article-title":"Neurodegeneration and inflammation-an interesting interplay in parkinson's disease","volume":"21","author":"Marogianni","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2020.08.015","article-title":"Acupuncture inhibits neuroinflammation and gut microbial dysbiosis in a mouse model of Parkinson's disease","volume":"89","author":"Jang","year":"2020","journal-title":"Brain Behav Immun"},{"key":"B14","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1111\/cns.13784","article-title":"Electroacupuncture ameliorates postoperative cognitive dysfunction and associated neuroinflammation via NLRP3 signal inhibition in aged mice","volume":"28","author":"Sun","year":"2022","journal-title":"CNS Neurosci Ther"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3390\/healthcare10112334","article-title":"Effectiveness of acupuncture in parkinson's disease symptoms-A systematic review","volume":"10","author":"Pereira","year":"2022","journal-title":"Healthcare (Basel)"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000005836","article-title":"Clinical effectiveness of acupuncture on Parkinson disease: A PRISMA-compliant systematic review and meta-analysis","volume":"96","author":"Lee","year":"2017","journal-title":"Med (Baltimore)"},{"key":"B17","doi-asserted-by":"publisher","first-page":"9926445","DOI":"10.1155\/2021\/9926445","article-title":"Acupuncture for parkinson's disease: efficacy evaluation and mechanisms in the dopaminergic neural circuit","volume":"2021","author":"Zhao","year":"2021","journal-title":"Neural Plast"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci13040541","article-title":"Electroacupuncture at Fengchi(GB20) and Yanglingquan(GB34) Ameliorates Paralgesia through Microglia-Mediated Neuroinflammation in a Rat Model of Migraine","volume":"13","author":"Zhou","year":"2023","journal-title":"Brain Sci"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2021.676827","article-title":"Acupuncture-related therapies for parkinson's disease: A meta-analysis and qualitative review","volume":"13","author":"Wen","year":"2021","journal-title":"Front Aging Neurosci"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2017.12.006","article-title":"Synergistic immunoreaction of acupuncture-like dissolving microneedles containing thymopentin at acupoints in immune-suppressed rats","volume":"8","author":"Zhang","year":"2018","journal-title":"Acta Pharm Sin B"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1039\/D1BM01249E","article-title":"Microneedle-mediated transdermal nanodelivery systems: a review","volume":"9","author":"Ruan","year":"2021","journal-title":"Biomater Sci"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2021.02.010","article-title":"Microneedle-based devices for point-of-care infectious disease diagnostics","volume":"11","author":"Dixon","year":"2021","journal-title":"Acta Pharm Sin B"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1111\/srt.13413","article-title":"Development of a novel microneedle platform for biomarker assessment of atopic dermatitis patients","volume":"29","author":"Lee","year":"2023","journal-title":"Skin Res Technol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2013.05.026","article-title":"Droplet-born air blowing: novel dissolving microneedle fabrication","volume":"170","author":"Kim","year":"2013","journal-title":"J Control Release"},{"key":"B25","doi-asserted-by":"publisher","first-page":"109184","DOI":"10.1016\/j.biopha.2019.109184","article-title":"Protective effects of DA-9805 on dopaminergic neurons against 6-hydroxydopamine-induced neurotoxicity in the models of Parkinson's disease","volume":"117","author":"Eo","year":"2019","journal-title":"BioMed Pharmacother"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.4062\/biomolther.2021.077","article-title":"Botulinum toxin A ameliorates neuroinflammation in the MPTP and 6-OHDA-induced parkinson's disease models","volume":"30","author":"Ham","year":"2022","journal-title":"Biomol Ther (Seoul)"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-4328(01)00309-6","article-title":"Behavioral phenotyping of the MPTP mouse model of Parkinson's disease","volume":"125","author":"Sedelis","year":"2001","journal-title":"Behav Brain Res"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2017.49","article-title":"Reassessment of subacute MPTP-treated mice as animal model of Parkinson's disease","volume":"38","author":"Zhang","year":"2017","journal-title":"Acta Pharmacol Sin"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.21769\/BioProtoc.3337","article-title":"Cylinder test to assess sensory-motor function in a mouse model of parkinson's disease","volume":"9","author":"Magno","year":"2019","journal-title":"Bio Protoc"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.21203\/rs.3.rs-4515123\/v1","article-title":"Nicotinamide adenine dinucleotide does not improve anesthetic recovery in rodents","author":"Goodnough","year":"2024","journal-title":"Res Sq"},{"key":"B31","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.nutres.2021.09.003","article-title":"Tocotrienols protect differentiated SH-SY5Y human neuroblastoma cells against 6-hydroxydopamine-induced cytotoxicity by ameliorating dopamine biosynthesis and dopamine receptor D2 gene expression","volume":"98","author":"Magalingam","year":"2022","journal-title":"Nutr Res"},{"key":"B32","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1186\/s12974-023-02966-9","article-title":"Inhibition of microfold cells ameliorates early pathological phenotypes by modulating microglial functions in Alzheimer's disease mouse model","volume":"20","author":"Kim","year":"2023","journal-title":"J Neuroinflamm"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(87)90021-2","article-title":"Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction","volume":"162","author":"Chomczynski","year":"1987","journal-title":"Anal Biochem"},{"key":"B34","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1186\/s12974-021-02296-8","article-title":"T-cell dysregulation is associated with disease severity in Parkinson's Disease","volume":"18","author":"Bhatia","year":"2021","journal-title":"J Neuroinflamm"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3109\/08923973.2015.1070172","article-title":"6-Hydroxydopamine as a tool to understand adaptive immune system-induced dopamine neurodegeneration in Parkinson's disease","volume":"37","author":"Theodore","year":"2015","journal-title":"Immunopharmacol Immunotoxicol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2005.04281.x","article-title":"6-Hydroxydopamine-induced alterations in blood-brain barrier permeability","volume":"22","author":"Carvey","year":"2005","journal-title":"Eur J Neurosci"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2019.07.026","article-title":"IL-17A exacerbates neuroinflammation and neurodegeneration by activating microglia in rodent models of Parkinson's disease","volume":"81","author":"Liu","year":"2019","journal-title":"Brain Behav Immun"},{"key":"B38","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1038\/s41531-023-00471-7","article-title":"Peripheral inflammatory immune response differs among sporadic and familial Parkinson's disease","volume":"9","author":"Munoz-Delgado","year":"2023","journal-title":"NPJ Parkinsons Dis"},{"key":"B39","doi-asserted-by":"publisher","first-page":"105700","DOI":"10.1016\/j.nbd.2022.105700","article-title":"Immune responses in the Parkinson's disease brain","volume":"168","author":"Weiss","year":"2022","journal-title":"Neurobiol Dis"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.rvsc.2007.04.004","article-title":"A proposed transpositional acupoint system in a mouse and rat model","volume":"84","author":"Yin","year":"2008","journal-title":"Res Vet Sci"},{"key":"B41","first-page":"67","article-title":"Jae-Hyo Kim, Dae-Hwan Youn,Bong-Hyo Lee, Youn-Byoung Chae, Il-Hwan Choi, Sun-Mi Choi, Acupuncture point locations for experimental animal studies in rats and mice","volume":"27","author":"Sung-Tae Koo","year":"2010","journal-title":"Korean J acupuncture"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3233\/THC-228048","article-title":"Data mining-based detection of the clinical effect on motion style acupuncture therapy combined with conventional acupuncture therapy in chronic neck pain","volume":"30","author":"Lyu","year":"2022","journal-title":"Technol Health Care"},{"key":"B43","doi-asserted-by":"publisher","first-page":"9512875","DOI":"10.1155\/2019\/9512875","article-title":"Effect of electroacupuncture on hyperalgesia and vasoactive neurotransmitters in a rat model of conscious recurrent migraine","volume":"2019","author":"Xu","year":"2019","journal-title":"Evid Based Complement Alternat Med"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.668616","article-title":"Determining 5HT(7)R's involvement in modifying the antihyperalgesic effects of electroacupuncture on rats with recurrent migraine","volume":"15","author":"Liu","year":"2021","journal-title":"Front Neurosci"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-020-0344-4","article-title":"Parkinson disease and the immune system - associations, mechanisms and therapeutics","volume":"16","author":"Tan","year":"2020","journal-title":"Nat Rev Neurol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3389\/fnana.2014.00084","article-title":"Striatal vessels receive phosphorylated tyrosine hydroxylase-rich innervation from midbrain dopaminergic neurons","volume":"8","author":"Afonso-Oramas","year":"2014","journal-title":"Front Neuroanat"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.3390\/cells11050860","article-title":"Mast cells and acupuncture analgesia","volume":"11","author":"Li","year":"2022","journal-title":"Cells"},{"key":"B48","doi-asserted-by":"publisher","first-page":"13921","DOI":"10.1038\/s41598-018-32048-3","article-title":"Neuropeptide initiated mast cell activation by transcutaneous electrical acupoint stimulation of acupoint LI4 in rats","volume":"8","author":"Chen","year":"2018","journal-title":"Sci Rep"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1454102\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T05:10:32Z","timestamp":1731993032000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1454102\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,19]]},"references-count":48,"alternative-id":["10.3389\/fimmu.2024.1454102"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2024.1454102","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,19]]},"article-number":"1454102"}}