{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T04:58:03Z","timestamp":1790485083410,"version":"4.1.0"},"reference-count":23,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation","award":["82260336"],"award-info":[{"award-number":["82260336"]}]},{"name":"National Natural Science Foundation","award":["82560336"],"award-info":[{"award-number":["82560336"]}]},{"name":"Joint Special Project of the Yunnan Provincial Applied Basic Research Program","award":["202301AY070001-267"],"award-info":[{"award-number":["202301AY070001-267"]}]},{"name":"Joint Special Project of the Yunnan Provincial Applied Basic Research Program","award":["202301AY070001-234"],"award-info":[{"award-number":["202301AY070001-234"]}]},{"name":"Joint Special Project of the Yunnan Provincial Applied Basic Research Program","award":["202301AY070001-026"],"award-info":[{"award-number":["202301AY070001-026"]}]},{"name":"Joint Special Project of the Yunnan Provincial Applied Basic Research Program","award":["202301AY070001-002"],"award-info":[{"award-number":["202301AY070001-002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Methamphetamine (METH) exposure induces neuroinflammation and cognitive impairment, yet the molecular signals that convert neuronal stress into microglial inflammatory activation remain unclear. This study investigated whether disruption of the CX3CL1\/CX3CR1 signaling contributes to METH-induced injury in the prefrontal cortex (PFC). C57BL\/6J mice were exposed to METH and assessed for behavioral changes using Y-maze, novel object recognition, and open-field tests. Neuronal injury was evaluated by Nissl staining, and CX3CL1, CX3CR1, and inflammatory mediators were quantified by Western blotting, immunofluorescence, and enzyme-linked immunosorbent assay. Mechanistic validation was performed using neuronal CX3CL1 overexpression and microglial CX3CR1 knockdown models, together with HT-22 neuronal-like cells and BV2 microglial cells in monoculture and coculture systems. METH exposure impaired cognitive performance, increased locomotor activity, induced neuronal injury, and intensified neuroinflammatory signaling. These changes were accompanied by decreased neuronal CX3CL1 and increased microglial CX3CR1 in the PFC, indicating dysregulation of the CX3CL1\/CX3CR1 axis. CX3CL1 overexpression partially attenuated METH-induced CX3CR1 upregulation and reduced neuroinflammatory injury, whereas CX3CR1 knockdown suppressed microglial inflammatory activation and improved behavioral outcomes. These findings suggest that CX3CL1\/CX3CR1 dysregulation may contribute to METH-induced disruption of neuron\u2013microglia crosstalk and neuroinflammation-associated cognitive impairment.<\/jats:p>","DOI":"10.3390\/ijms27198576","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T10:34:10Z","timestamp":1790332450000},"page":"8576","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CX3CL1\/CX3CR1-Mediated Neuron\u2013Microglia Crosstalk Contributes to Methamphetamine-Induced Neuroinflammation and Cognitive Impairment"],"prefix":"10.3390","volume":"27","author":[{"given":"Zhiwen","family":"Wang","sequence":"first","affiliation":[{"name":"National Health Commission Key Laboratory of Drug Addiction Medicine, School of Forensic Medicine, Kunming Medical University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Genmeng","family":"Yang","sequence":"additional","affiliation":[{"name":"National Health Commission Key Laboratory of Drug Addiction Medicine, School of Forensic Medicine, Kunming Medical University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Ziyan","family":"Zhu","sequence":"additional","affiliation":[{"name":"National Health Commission Key Laboratory of Drug Addiction Medicine, School of Forensic Medicine, Kunming Medical University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Ruike","family":"Xu","sequence":"additional","affiliation":[{"name":"National Health Commission Key Laboratory of Drug Addiction Medicine, School of Forensic Medicine, Kunming Medical University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Xiong","family":"Wei","sequence":"additional","affiliation":[{"name":"National Health Commission Key Laboratory of Drug Addiction Medicine, School of Forensic Medicine, Kunming Medical University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Yunlan","family":"Li","sequence":"additional","affiliation":[{"name":"National Health Commission Key Laboratory of Drug Addiction Medicine, School of Forensic Medicine, Kunming Medical University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3186-734X","authenticated-orcid":false,"given":"Shijun","family":"Hong","sequence":"additional","affiliation":[{"name":"National Health Commission Key Laboratory of Drug Addiction Medicine, School of Forensic Medicine, Kunming Medical University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Yanxia","family":"Peng","sequence":"additional","affiliation":[{"name":"National Health Commission Key Laboratory of Drug Addiction Medicine, School of Forensic Medicine, Kunming Medical University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/s10571-026-01747-1","article-title":"Molecular Mechanisms of Hippocampal Synaptic Plasticity Disruption Induced by Chronic Methamphetamine Exposure: A Narrative Review","volume":"46","author":"Razazpour","year":"2026","journal-title":"Cell. 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