{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T05:16:07Z","timestamp":1789103767446,"version":"build-2803163510"},"reference-count":50,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,1,5]],"date-time":"2022-01-05T00:00:00Z","timestamp":1641340800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Neuronal hyperactivity is an early neuronal defect commonly observed in familial and sporadic Alzheimer's disease (AD), but the underlying mechanisms are unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We employed a ryanodine receptor 2 (RyR2) mutant mouse model harboring the R4496C<jats:sup>+\/\u2013<\/jats:sup> mutation that markedly increases the channel's open probability (Po) to determine the impact of increased RyR2 activity in neuronal function without AD gene mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Genetically increasing RyR2 Po induced neuronal hyperactivity in vivo in anesthetized and awake mice. Increased RyR2 Po induced hyperactive behaviors, impaired learning and memory, defective dendritic spines, and neuronal cell death. Increased RyR2 Po exacerbated the onset of neuronal hyperexcitability and learning and memory impairments in 5xFAD mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Increased RyR2 Po exacerbates the onset of familial AD\u2013associated neuronal dysfunction, and induces AD\u2010like defects in the absence of AD\u2010causing gene mutations, suggesting that RyR2\u2010associated neuronal hyperactivity represents a common target for combating AD with or without AD gene mutations.<\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.12543","type":"journal-article","created":{"date-parts":[[2022,1,5]],"date-time":"2022-01-05T06:49:55Z","timestamp":1641365395000},"page":"2088-2098","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Increased RyR2 open probability induces neuronal hyperactivity and memory loss with or without Alzheimer's disease\u2013causing gene mutations"],"prefix":"10.1002","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4602-7159","authenticated-orcid":false,"given":"Jinjing","family":"Yao","sequence":"first","affiliation":[{"name":"Libin Cardiovascular Institute Department of Physiology and Pharmacology Cumming School of Medicine University of Calgary  Calgary Alberta Canada"},{"name":"Hotchkiss Brain Institute Department of Physiology and Pharmacology Cumming School of Medicine University of Calgary  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajing","family":"Liu","sequence":"additional","affiliation":[{"name":"Libin Cardiovascular Institute Department of Physiology and Pharmacology Cumming School of Medicine University of Calgary  Calgary Alberta Canada"},{"name":"Department of Pharmacology Shenyang Pharmaceutical University  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Sun","sequence":"additional","affiliation":[{"name":"Libin Cardiovascular Institute Department of Physiology and Pharmacology Cumming School of Medicine University of Calgary  Calgary Alberta Canada"},{"name":"Medical School Kunming University of Science and Technology  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqin","family":"Zhan","sequence":"additional","affiliation":[{"name":"Hotchkiss Brain Institute Department of Cell Biology and Anatomy Cumming School of Medicine University of Calgary  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John Paul","family":"Estillore","sequence":"additional","affiliation":[{"name":"Libin Cardiovascular Institute Department of Physiology and Pharmacology Cumming School of Medicine University of Calgary  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ray W.","family":"Turner","sequence":"additional","affiliation":[{"name":"Hotchkiss Brain Institute Department of Cell Biology and Anatomy Cumming School of Medicine University of Calgary  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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