A comparison of cognitive decline in aged mice and mice treated with aftin-4

Žnidaršič, Neža (author), Grgurevič, Neža (author), Nemec Svete, Alenka (author), Meden, Anže (author), Snoj, Tomaž (author)

Dementia, especially Alzheimer’s disease, presents a major clinical challenge, and researchers are still searching for an optimal animal model. To address this gap, we compared male and ovariectomized female C57BL/6 mice treated with 30 mg/kg aftin-4, which induces neurodegeneration, with naturally aged (15–16 months old) mice not treated with aftin-4. We performed a series of behavioral tests; measured postmortem plasma β-amyloid levels (Aβ1–40 and Aβ1–42) and the levels of the oxidative stress indicators glutathione peroxidase (GPx), superoxide dismutase (SOD) and malondialdehyde (MDA); and evaluated astrocytic reactivity in the brain using glial fibrillary acid protein (GFAP) levels. Our results revealed no behavioral changes in the aged or aftin-4-treated mice compared with the control mice. Aftin-4 mice presented lower brain MDA levels and no detectable changes in plasma Aβ levels. In general, female mice had higher GPx and SOD levels and lower Aβ1–42 levels than male mice did. In contrast, aged and aftin-4-treated male mice presented elevated levels of GFAP, indicating astrocyte damage. Our results could not confirm that either aftin-4-treated or aged mice are reliable models for dementia. However, the observed molecular changes suggest that male animals may be more susceptible to oxidative stress and brain damage than females are. This study demonstrates the complexity of modeling dementia in animals and the importance of future studies in this area.

• Language: English
• Keywords: aftin-4, aged mice, cognitive decline, oxidative stress, animal behavior, drug discovery, neuroscience
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: VF - Veterinary Faculty; FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2024
• Number of pages: 16 str.
• Numbering: Vol. 14, art. 28320
• PID: 20.500.12556/RUL-165234
• UDC: 636.09:616
• ISSN on article: 2045-2322
• DOI: 10.1038/s41598-024-79792-3
• COBISS.SI-ID: 215571459
• Publication date in RUL: 27.11.2024

Record is a part of a journal

• Title: Scientific reports
• Shortened title: Sci. rep.
• Publisher: Nature Publishing Group
• ISSN: 2045-2322
• COBISS.SI-ID: 18727432

Licences

• License: CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
• Link: http://creativecommons.org/licenses/by-nc-nd/4.0/
• Description: The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.

Projects

• Funder: ARIS - Slovenian Research and Innovation Agency
• Funding programme: Young researchers

• Funder: ARIS - Slovenian Research and Innovation Agency
• Project number: P4-0053
• Name: Endokrini, imunski in encimski odzivi pri zdravih in bolnih živalih