{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T15:01:29Z","timestamp":1788620489334,"version":"build-2803163510"},"reference-count":77,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002426","name":"Fondazione Telethon","doi-asserted-by":"publisher","award":["GMR23T1234"],"award-info":[{"award-number":["GMR23T1234"]}],"id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Astrocytes are essential gatekeepers of brain homeostasis, and the disruption of their functions can contribute to the development of several neurological diseases. Among astrocyte signaling pathways, the intracellular second messenger Ca2+ plays a pivotal role in regulating the release of gliotransmitters, which actively modulate fundamental processes in the brain such as synaptic plasticity and memory function. Several studies over the years support the idea that dysregulated astrocytic Ca2+ homeostasis represents a relevant mechanism in Alzheimer\u2019s disease pathogenesis. Early works in transgenic mice modelling Alzheimer\u2019s disease reported increased Ca2+ activity in astroglial cells, supporting the idea of hyperactivity as a common trait of astrocytes in this pathology. However, recent studies have described astrocyte Ca2+ hypoactivity in various mouse models, revealing a more complex and heterogeneous scenario. In this review, we summarize and critically discuss the main studies addressing the direction(s) of astrocytic Ca2+ signaling dysfunction in mouse models of Alzheimer\u2019s disease. We prioritize investigations performed in ex vivo and in vivo conditions, carefully comparing the different experimental approaches used to measure Ca2+ activity in astrocytes. By integrating results across multiple mouse models and methodological strategies, we aim to provide a more complete picture of astrocyte Ca2+ dysregulation in Alzheimer\u2019s disease.<\/jats:p>","DOI":"10.3390\/biom16030404","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T08:43:31Z","timestamp":1773132211000},"page":"404","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Astrocyte Ca2+ Dysregulation in Alzheimer\u2019s Disease Mouse Models: Revisiting the Dogma of Hyperactivity"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1426-4440","authenticated-orcid":false,"given":"Alessandro","family":"Di Spiezio","sequence":"first","affiliation":[{"name":"Neuroscience Institute, National Research Council (CNR), 35131 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9982-6405","authenticated-orcid":false,"given":"Micaela","family":"Zonta","sequence":"additional","affiliation":[{"name":"Neuroscience Institute, National Research Council (CNR), 35131 Padua, Italy"},{"name":"Padova Neuroscience Center, University of Padua, 35129 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"ra26","DOI":"10.1126\/scisignal.2002334","article-title":"Astrocytes Modulate Neural Network Activity by Ca2+-Dependent Uptake of Extracellular K+","volume":"5","author":"Wang","year":"2012","journal-title":"Sci. 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