{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:17Z","timestamp":1787028557073,"version":"build-2736575974"},"reference-count":137,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T00:00:00Z","timestamp":1739491200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Aging and age-related neurodegenerative disorders are characterized by the dysfunction or loss of brain nicotinic acetylcholine receptors (nAChRs), and these changes may be related to other senescence markers, such as oxidative stress and DNA repair dysfunction. However, the mechanism of nAChR loss in the aging brain and the modification of this process by drugs (e.g., memantine, Mem) are not yet fully understood. To study whether the differences in nAChR expression in the rat brain occur due to aging or oxidative stress and are modulated by Mem, we analyzed nAChR subunits (at RNA and protein levels) and other biomarkers by real-time quantitative polymerase chain reaction (RQ-PCR) and Western blot validation. Twenty-one female Wistar rats were divided into four groups, depending on age, and the oldest group received injections of Mem or water with the use of intragastric catheters. We studied the cerebral grey matter (CGM), subcortical white matter (SCWM), and cerebellum (Ce). Results showed an age-related decrease of \u03b17 nAChR mRNA level in SCWM. The \u03b17 nAChR mRNA loss was accompanied by reduced expression of 8-oxoguanine DNA glycosylase 1 (OGG1) and an increased tumor necrosis factor alpha (TNF\u03b1) level. In the water group, we observed a higher level of \u03b17 nAChR protein in the SCWM and Ce. Biomarker levels changed, but to a different extent depending on the brain area. Importantly, the dysfunction in antioxidative status was stopped and even regressed under Mem treatment. After two weeks of treatment, an increase in TP53 protein level and a decrease in 8-oxo-2\u2032deoxyguanosine (8-oxo-2\u2032dG) level were observed. We conclude that Mem administration may be protective against the senescence process by antioxidative mechanisms.<\/jats:p>","DOI":"10.3390\/ijms26041634","type":"journal-article","created":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T06:52:01Z","timestamp":1739515921000},"page":"1634","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Expression of Neuronal Nicotinic Acetylcholine Receptor and Early Oxidative DNA Damage in Aging Rat Brain\u2014The Effects of Memantine"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8613-4955","authenticated-orcid":false,"given":"Ma\u0142gorzata Anna","family":"Lewandowska","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Poznan Medical University, 55 Bulgarska St., 60-320 Poznan, Poland"},{"name":"Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, 6 \u015awiecickiego St., 60-781 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1544-5956","authenticated-orcid":false,"given":"Agata","family":"R\u00f3\u017cycka","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, 6 \u015awiecickiego St., 60-781 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2815-0372","authenticated-orcid":false,"given":"Teresa","family":"Grzelak","sequence":"additional","affiliation":[{"name":"Department of Physiology, Poznan University of Medical Sciences, 6 \u015awiecickiego St., 60-781 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bartosz","family":"Kempisty","sequence":"additional","affiliation":[{"name":"Department of Human Morphology and Embryology, Division of Anatomy, Wroc\u0142aw Medical University, 50-368 Wroclaw, Poland"},{"name":"Institute of Veterinary Medicine, Nicolaus Copernicus University, 87-100 Torun, Poland"},{"name":"Physiology Graduate Faculty, North Carolina State University, Raleigh, NC 27695, USA"},{"name":"Center of Assisted Reproduction, Department of Obstetrics and Gynecology, University Hospital and Masaryk University, 625 00 Brno, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9046-6802","authenticated-orcid":false,"given":"Pawe\u0142 Piotr","family":"Jagodzi\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, 6 \u015awiecickiego St., 60-781 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4122-7469","authenticated-orcid":false,"given":"Margarita","family":"Lianeri","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, 6 \u015awiecickiego St., 60-781 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8241-0403","authenticated-orcid":false,"given":"Jolanta","family":"Dorszewska","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology, Department of Neurology, Poznan University of Medical Sciences, 49 Przybyszewskiego St., 60-355 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Mohamed, W.M.Y., Yi, C., Soreq, L., and Yamashita, T. 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