{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T15:15:29Z","timestamp":1790262929887,"version":"4.1.0"},"reference-count":112,"publisher":"SAGE Publications","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2023,1,3]]},"abstract":"<jats:p>Background: Alzheimer\u2019s disease (AD) is a chronic neurodegenerative disorder with a progressive loss of cognitive function. Currently, no effective treatment regimen is available. Lithium, a mood stabilizer for bipolar disorder, exerts broad neuroprotective and neurotrophic actions and improves cognitive function. Objective: The study investigated if lithium stabilizes Ca2+ signaling abnormalities in hippocampal neurons and subsequently normalize downstream effects on AD neuropathology and synaptic plasticity in young AD mice. Methods: Four-month-old 3xTg-AD mice were treated with a LiCl diet chow for 30 days. At the end of the lithium treatment, a combination of two-photon Ca2+ imaging, electrophysiology, and immunohistochemistry assays were used to assess the effects of the LiCl treatment on inositol trisphosphate receptor (IP3R)-dependent endoplasmic reticulum (ER) Ca2+ and voltage-gated Ca2+ channel (VGCC)-mediated Ca2+ signaling in CA1 neurons, neuronal nitric oxide synthase (nNOS) and hyperphosphorylated tau (p-tau) levels and synaptic plasticity in the hippocampus and overlying cortex from 3xTg-ADmice. Results: Thirty-day LiCl treatment reduced aberrant IP3R-dependent ER Ca2+ and VGCC-mediated Ca2+ signaling in CA1 pyramidal neurons from 3xTg-AD mice and restored neuronal nitric oxide synthase (nNOS) and hyperphosphorylated tau (p-tau) levels to control levels in the hippocampal subfields and overlying cortex. The LiCl treatment enhanced post-tetanic potentiation (PTP), a form of short-term plasticity in the hippocampus. Conclusion: The study found that lithium exerts therapeutic effects across several AD-associated early neuronal signaling abnormalities including aberrant Ca2+ signaling, nNOS, and p-tau formation and enhances short-term synaptic plasticity. Lithium could serve as an effective treatment or co-therapeutic for AD.<\/jats:p>","DOI":"10.3233\/jad-220758","type":"journal-article","created":{"date-parts":[[2022,11,25]],"date-time":"2022-11-25T09:59:23Z","timestamp":1669370363000},"page":"273-290","source":"Crossref","is-referenced-by-count":21,"title":["Lithium Provides Broad Therapeutic Benefits in an Alzheimer\u2019s Disease Mouse Model"],"prefix":"10.1177","volume":"91","author":[{"given":"Alyssa L.","family":"Wiseman","sequence":"first","affiliation":[{"name":"Discipline of Neuroscience, The Chicago Medical School, Rosalind Franklin University, North Chicago, IL, USA"},{"name":"School of Graduate and Postdoctoral Studies, Rosalind Franklin University, North Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clark A.","family":"Briggs","sequence":"additional","affiliation":[{"name":"Discipline of Neuroscience, The Chicago Medical School, Rosalind Franklin University, North Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariel","family":"Peritt","sequence":"additional","affiliation":[{"name":"Discipline of Neuroscience, The Chicago Medical School, Rosalind Franklin University, North Chicago, IL, USA"},{"name":"Sackler School of Medicine, New York State\/American Program of Tel Aviv University, Tel Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Kapecki","sequence":"additional","affiliation":[{"name":"Discipline of Neuroscience, The Chicago Medical School, Rosalind Franklin University, North Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel A.","family":"Peterson","sequence":"additional","affiliation":[{"name":"Center for Neurodegenerative Disease and Therapeutics, Rosalind Franklin University, North Chicago, IL, USA"},{"name":"Discipline of Neuroscience, The Chicago Medical School, Rosalind Franklin University, North Chicago, IL, USA"},{"name":"School of Graduate and Postdoctoral Studies, Rosalind Franklin University, North Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong S.","family":"Shim","sequence":"additional","affiliation":[{"name":"Discipline of Psychiatry and Behavioral Sciences, The Chicago Medical School, Rosalind Franklin University, North Chicago, IL, USA"},{"name":"Captain James A. 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