{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T19:26:01Z","timestamp":1793388361020,"version":"4.5.0"},"reference-count":237,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:p>\n                    Microglia, the innate immune cells of the central nervous system (CNS), play essential roles in maintaining neural homeostasis through dynamic interactions with neurons and other brain structures. While their protective functions are well-established, recent studies have illuminated the detrimental consequences of sustained microglial activation in the context of neurodegeneration. In particular, overactivated microglia contribute to neuroinflammation and induce synaptic alterations through the release of pro-inflammatory cytokines and engagement of specific receptors. These interactions disrupt synaptic structure and function, compromising connectivity, plasticity, and cognitive processes. Notably, neuronal synapses are primary targets of such inflammation-driven dysfunction, where prolonged exposure to cytokines such as interleukin-1\u03b2 (IL-1\u03b2), interleukin-6 (IL-6), and tumor necrosis factor-\n                    <jats:italic>\u03b1<\/jats:italic>\n                    (TNF-\u03b1), and signaling via receptor systems including cluster of differentiation-200 (CD200)\/CD200 receptor (CD200R), C-X3-C motif chemokine ligand 1 (CX3CL1)\/CX3C receptor 1 (CX3CR1), colony-stimulating factor 1 (CSF1)\/CSF1 receptor (CSF1R), and interferon-\n                    <jats:italic>\u03b3<\/jats:italic>\n                    (IFN-\u03b3)\/IFN-\u03b3 receptor (IFN-\u03b3R), lead to impaired learning, excitotoxicity, and neurodegenerative progression. This review synthesizes emerging evidence on the mechanisms by which microglia-mediated immune responses regulate synaptic remodeling, emphasizing the roles of pro-inflammatory cytokines and their receptors in neurodegenerative disorders.\n                  <\/jats:p>","DOI":"10.3389\/fncel.2025.1700692","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T06:31:13Z","timestamp":1762756273000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":97,"title":["Microglia-orchestrated neuroinflammation and synaptic remodeling: roles of pro-inflammatory cytokines and receptors in neurodegeneration"],"prefix":"10.3389","volume":"19","author":[{"given":"Guang","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waimao","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,10]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2633105520947081","DOI":"10.1177\/2633105520947081","article-title":"Interferon-gamma and interleukin-1Beta enhance the secretion of brain-derived neurotrophic factor and promotes the survival of cortical neurons in brain injury","volume":"15","author":"Abd-El-Basset","year":"2020","journal-title":"Neurosci Insights"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"eaav3577","DOI":"10.1126\/scisignal.aav3577","article-title":"BDNF increases synaptic NMDA receptor abundance by enhancing the local translation of Pyk2 in cultured hippocampal neurons","volume":"12","author":"Afonso","year":"2019","journal-title":"Sci Signal"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.molimm.2020.12.035","article-title":"TREM2 alters the phagocytic, apoptotic and inflammatory response to Abeta42 in HMC3 cells","volume":"131","author":"Akhter","year":"2021","journal-title":"Mol. 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