Institute of Preclinical Sciences, Veterinary Faculty, University of Ljubljana, Gerbičeva 60, Ljubljana, 1000, Slovenia.
Small Animal Clinic, Veterinary Faculty, University of Ljubljana, Gerbičeva 60, Ljubljana, 1000, Slovenia.
Sci Rep. 2024 Nov 16;14(1):28320. doi: 10.1038/s41598-024-79792-3.
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.
痴呆症，特别是阿尔茨海默病，是一个重大的临床挑战，研究人员仍在寻找最佳的动物模型。为了弥补这一空白，我们比较了经 30mg/kg aftin-4 处理的雄性和去卵巢雌性 C57BL/6 小鼠与未经 aftin-4 处理的自然衰老（15-16 月龄）小鼠。我们进行了一系列行为测试；测量了死后血浆 β-淀粉样蛋白水平（Aβ1-40 和 Aβ1-42）和氧化应激指标谷胱甘肽过氧化物酶（GPx）、超氧化物歧化酶（SOD）和丙二醛（MDA）的水平；并用胶质纤维酸性蛋白（GFAP）水平评估了大脑中的星形胶质细胞反应性。我们的结果显示，与对照组相比，年老或 aftin-4 处理的小鼠没有行为变化。aftin-4 小鼠的大脑 MDA 水平较低，血浆 Aβ 水平没有检测到变化。总的来说，雌性小鼠的 GPx 和 SOD 水平较高，Aβ1-42 水平较低。相比之下，年老和 aftin-4 处理的雄性小鼠呈现出较高的 GFAP 水平，表明星形胶质细胞受损。我们的结果不能证实 aftin-4 处理或年老的小鼠是痴呆症的可靠模型。然而，观察到的分子变化表明，雄性动物可能比雌性动物更容易受到氧化应激和大脑损伤的影响。本研究表明了在动物中模拟痴呆症的复杂性，以及在该领域进行未来研究的重要性。
