{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T20:12:56Z","timestamp":1776802376817,"version":"3.51.2"},"reference-count":64,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,10,25]],"date-time":"2024-10-25T00:00:00Z","timestamp":1729814400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017074","name":"Zinpro","doi-asserted-by":"publisher","award":["6128"],"award-info":[{"award-number":["6128"]}],"id":[{"id":"10.13039\/100017074","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011669","name":"International Zinc Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011669","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Astrocytes are important regulators of neuronal development and activity. Their activation plays a key role in the response to many central nervous system (CNS) pathologies. However, reactive astrocytes are a double\u2010edged sword as their chronic or excessive activation may negatively impact CNS physiology, for example, via abnormal modulation of synaptogenesis and synapse function. Accordingly, astrocyte activation has been linked to neurodegenerative and neurodevelopmental disorders. Therefore, the attenuation of astrocyte activation may be an important approach for preventing and treating these disorders. Since zinc deficiency has been consistently linked to increased pro\u2010inflammatory signaling, we aimed to identify cellular zinc\u2010dependent signaling pathways that may lead to astrocyte activation using techniques such as immunocytochemistry and protein biochemistry to detect astrocyte GFAP expression, fluorescent imaging to detect oxidative stress levels in activated astrocytes, cytokine profiling, and analysis of primary neurons subjected to astrocyte secretomes. Our results reveal a so far not well\u2010described pathway in astrocytes, the platelet activation factor receptor (PAFR) pathway, as a critical zinc\u2010dependent signaling pathway that is sufficient to control astrocyte reactivity. Low zinc levels activate PAFR signaling\u2010driven crosstalk between astrocytes and neurons, which alters excitatory synapse formation during development in a PAFR\u2010dependent manner. We conclude that zinc is a crucial signaling ion involved in astrocyte activation and an important dietary factor that controls astrocytic pro\u2010inflammatory processes. Thus, targeting zinc homeostasis may be an important approach in several neuroinflammatory conditions.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc16252-fig-0005-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.16252","type":"journal-article","created":{"date-parts":[[2024,10,25]],"date-time":"2024-10-25T06:26:08Z","timestamp":1729837568000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Zinc signaling controls astrocyte\u2010dependent synapse modulation via the\n                    <scp>PAF<\/scp>\n                    receptor pathway"],"prefix":"10.1111","volume":"169","author":[{"given":"Janelle E.","family":"Stanton","sequence":"first","affiliation":[{"name":"Bernal Institute University of Limerick  Limerick Ireland"},{"name":"Department of Biological Sciences University of Limerick  Limerick Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sakshi","family":"Hans","sequence":"additional","affiliation":[{"name":"Bernal Institute University of Limerick  Limerick Ireland"},{"name":"Department of Biological Sciences University of Limerick  Limerick Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ioannis","family":"Zabetakis","sequence":"additional","affiliation":[{"name":"Bernal Institute University of Limerick  Limerick Ireland"},{"name":"Department of Biological Sciences University of Limerick  Limerick Ireland"},{"name":"Health Research Institute (HRI) University of Limerick  Limerick 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