{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T02:12:23Z","timestamp":1782526343589,"version":"3.54.5"},"reference-count":78,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Synapsis Foundation Alzheimer Research Switzerland","award":["2020-PI06"],"award-info":[{"award-number":["2020-PI06"]}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation\n\t\t\t\t\t\t\t\t\t\t\t\t\t              https:\/\/ror.org\/00yjd3n13","doi-asserted-by":"publisher","award":["310030-212432"],"award-info":[{"award-number":["310030-212432"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Lausanne, Faculty of Biology and Medicine\n\t\t\t\t\t\t\t\t\t\t\t\t\t              https:\/\/ror.org\/019whta54"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Neuron-targeted therapies for Alzheimer\u2019s disease (AD) have shown limited efficacy, highlighting the need to explore glial-based mechanisms of neuroprotection. Here, we show that astrocyte mitochondrial uncoupling via viral overexpression of uncoupling protein 4 (UCP4) restores neuronal circuits and ion channel function in aged 3xTG AD mice with overt symptoms. Spontaneous local field potential recordings revealed a partial recovery of hippocampal and subicular sharp wave ripple oscillations, electrophysiological signatures of neuronal circuits known to be altered in AD. Combined whole-cell patch-clamp electrophysiology with two-photon Ca2+ imaging further demonstrated that UCP4 modulates activity-dependent Ca2+ influx, A-type potassium channel function, and enhances glial cell line-derived neurotrophic factor (GDNF) signaling. These findings identify astrocytic mitochondrial uncoupling as a potent mechanism enhancing neuronal resilience and restoring circuit function in symptomatic AD brains.<\/jats:p>","DOI":"10.3390\/cells15070597","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T15:45:42Z","timestamp":1774626342000},"page":"597","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Astrocyte Mitochondrial UCP4 Reprograms Neuronal Network Oscillations via GDNF-Dependent K+-Ca2+ Signaling in Alzheimer\u2019s Disease Mice"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4729-1883","authenticated-orcid":false,"given":"Aisylu","family":"Gaifullina","sequence":"first","affiliation":[{"name":"Department of Fundamental Neurosciences, University of Lausanne, CH-1005 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaima","family":"Belhi","sequence":"additional","affiliation":[{"name":"Department of Fundamental Neurosciences, University of Lausanne, CH-1005 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3709-5504","authenticated-orcid":false,"given":"Leonardo","family":"Restivo","sequence":"additional","affiliation":[{"name":"Department of Fundamental Neurosciences, University of Lausanne, CH-1005 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8911-0315","authenticated-orcid":false,"given":"Jean-Yves","family":"Chatton","sequence":"additional","affiliation":[{"name":"Department of Fundamental Neurosciences, University of Lausanne, CH-1005 Lausanne, Switzerland"},{"name":"Cellular Imaging Facility, University of Lausanne, CH-1005 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2430","DOI":"10.1002\/jnr.24075","article-title":"Astrocyte dysfunction in Alzheimer disease","volume":"95","author":"Acosta","year":"2017","journal-title":"J. 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