{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T03:51:18Z","timestamp":1785297078614,"version":"3.55.0"},"reference-count":52,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T00:00:00Z","timestamp":1727136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Fund of Bulgaria","award":["KP-06-H31\/16"],"award-info":[{"award-number":["KP-06-H31\/16"]}]},{"name":"National Science Fund of Bulgaria","award":["KP-06-H41\/4"],"award-info":[{"award-number":["KP-06-H41\/4"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In the search for Alzheimer\u2019s disease (AD) therapies, most animal models focus on familial AD, which accounts for a small fraction of cases. The majority of AD cases arise from stress factors, such as oxidative stress, leading to neurological changes (sporadic AD). Early in AD progression, dysfunction in \u03b3-secretase causes the formation of insoluble A\u03b21-42 peptides, which aggregate into senile plaques, triggering neurodegeneration, cognitive decline, and circadian rhythm disturbances. To better model sporadic AD, we used a new AD rat model induced by intracerebroventricular administration of A\u03b21-42 oligomers (icvA\u03b21-42) combined with melatonin deficiency via pinealectomy (pin). We validated this model by assessing spatial memory using the radial arm maze test and measuring A\u03b21-42 and \u03b3-secretase levels in the frontal cortex and hippocampus with ELISA. The icvA\u03b21-42 + pin model experienced impaired spatial memory and increased A\u03b21-42 and \u03b3-secretase levels in the frontal cortex and hippocampus, effects not seen with either icvA\u03b21-42 or the pin alone. Chronic melatonin treatment reversed memory deficits and reduced A\u03b21-42 and \u03b3-secretase levels in both structures. Our findings suggest that our icvA\u03b21-42 + pin model is extremely valuable for future AD research.<\/jats:p>","DOI":"10.3390\/ijms251910294","type":"journal-article","created":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T04:01:24Z","timestamp":1727236884000},"page":"10294","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Melatonin Supplementation Alleviates Impaired Spatial Memory by Influencing A\u03b21-42 Metabolism via \u03b3-Secretase in the icvA\u03b21-42 Rat Model with Pinealectomy"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1458-2457","authenticated-orcid":false,"given":"Irina","family":"Georgieva","sequence":"first","affiliation":[{"name":"Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Street, Block 21, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1640-5099","authenticated-orcid":false,"given":"Jana","family":"Tchekalarova","sequence":"additional","affiliation":[{"name":"Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Street, Block 23, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zlatina","family":"Nenchovska","sequence":"additional","affiliation":[{"name":"Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Street, Block 23, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidia","family":"Kortenska","sequence":"additional","affiliation":[{"name":"Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Street, Block 23, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6659-2588","authenticated-orcid":false,"given":"Rumiana","family":"Tzoneva","sequence":"additional","affiliation":[{"name":"Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Street, Block 21, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5481","DOI":"10.1038\/s41380-021-01249-0","article-title":"The Amyloid-\u03b2 Pathway in Alzheimer\u2019s Disease","volume":"26","author":"Hampel","year":"2021","journal-title":"Mol. 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