{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T06:13:09Z","timestamp":1793945589380,"version":"4.8.0"},"reference-count":21,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T00:00:00Z","timestamp":1764806400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Agency for Medical Research and Development (AMED) Core Research for Evolutionary medical Science and Technology","award":["23gm1510005h0003"],"award-info":[{"award-number":["23gm1510005h0003"]}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:p>\n                    Parkinson\u2019s disease (PD) and Alzheimer\u2019s disease (AD) present with complex behavioral symptoms that can arise in the absence of overt structural brain damage. Recent evidence suggests that border-associated macrophages (BAMs) located at the brain\u2019s interfaces regulate central nervous system function, yet the specific roles of distinct BAM subsets remain largely undefined. By reanalyzing single-nucleus RNA sequencing data from postmortem PD brains, we identified a BAM subset expressing CD169 that was significantly reduced in patients compared with controls. To examine their function, we employed CD169-DTR mice to selectively ablate CD169\n                    <jats:sup>+<\/jats:sup>\n                    BAMs and evaluated behavioral and histological changes. Depletion of CD169\n                    <jats:sup>+<\/jats:sup>\n                    BAMs induced tremors, abnormal hindlimb reflexes, and heightened anxiety-like behavior without dopaminergic neuron loss. Histological analysis revealed a pronounced reduction of mitral and tufted cells in the olfactory bulb, indicating disruption of olfactory-limbic circuitry. These findings demonstrate that CD169\n                    <jats:sup>+<\/jats:sup>\n                    BAMs are critical for maintaining neural network stability and motor function, and that their loss can elicit PD-like phenotypes in the absence of classical dopaminergic neurodegeneration. This work establishes a novel mouse model linking brain-border immune cell dysfunction to Parkinsonian pathology and highlights a neuroimmune mechanism that may contribute to the onset of PD-like disorders.\n                  <\/jats:p>","DOI":"10.3389\/fnins.2025.1688394","type":"journal-article","created":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T15:39:46Z","timestamp":1764862786000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Depletion of CD169+ border-associated macrophages induces Parkinson\u2019s disease-like behavior"],"prefix":"10.3389","volume":"19","author":[{"given":"Takuto","family":"Ohki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Kitamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuhiro","family":"Tokutake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sota","family":"Saeki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiro","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Takasu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Hirata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,4]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"263","DOI":"10.3389\/fimmu.2015.00263","article-title":"Much more than M1 and M2 macrophages, there are also CD169+ and TCR+ macrophages","volume":"6","author":"Chavez-Galan","year":"2015","journal-title":"Front. 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Autism."}],"container-title":["Frontiers in Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2025.1688394\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T15:39:46Z","timestamp":1764862786000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2025.1688394\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,4]]},"references-count":21,"alternative-id":["10.3389\/fnins.2025.1688394"],"URL":"https:\/\/doi.org\/10.3389\/fnins.2025.1688394","relation":{},"ISSN":["1662-453X"],"issn-type":[{"value":"1662-453X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,4]]},"article-number":"1688394"}}