Objective: It has been reported that D-galactose (D-gal) can model subacute aging, and aluminum (Al) acts as a neurotoxin, but combined effects of them have not been reported. The present work aimed to reveal the effect of combined administration of D-gal and Al in mice and compare the effect of D-gal treatment with that of Al treatment.
Methods: Al was intragastrically administered and D-gal was subcutaneously injected into Kunming mice for 10 consecutive weeks. Learning and memory, cholinergic systems, as well as protein levels of amyloid β (Aβ) and hyperphosphorylated tau were determined using Morri water maze test, biochemical assays and immunohistochemical staining, respectively.
Results: The mice with combined treatment had obvious learning and memory deficits, and showed decreases in brain acetylcholine (ACh) level and in activities of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE). Formation of senile plaque (SP)-like and neurofibrillary tangle (NFT)-like structures was also observed. The behavioral and pathological changes persisted for at least 6 weeks after withdrawal of D-gal and Al.
Conclusion: Combined use of D-gal and Al is an effective way to establish the non-transgenic Alzheimer's disease (AD) animal model, and is useful for studies of AD pathogenesis and therapeutic evaluation.
目的: D-半乳糖能制作亚急性衰老模型, 铝具有神经毒性, 但两者联合应用的作用未见报道。 本研究旨在探讨D-半乳糖和铝联合应用对动物学习记忆、 脑内生化和病理的影响, 以及与单独应用D-半乳糖或铝所制作的动物模型相比较。
方法|: 昆明小鼠单独皮下注射D-半乳糖、 单独灌胃铝以及既注射D-半乳糖又灌胃铝, 制作动物模型, 共给药8周或10周, 10周后再停用药物6周。 在第8、 10、 16周末, 采用Morris水迷宫检测小鼠学习记忆能力, 生化学方法检测脑内乙酰胆碱能系统, 免疫组化法检测老年斑和神经原纤维缠结的形成。
结果: 联合应用D-半乳糖和铝后, 小鼠表现出明显的学习和记忆力障碍, 并且其脑内乙酰胆碱水平降低, 乙酰胆碱转移酶和胆碱脂酶活性下降, 出现老年斑样和神经原纤维缠结样病理改变。 停止给药后, 其行为学、 生化和病理改变至少能维持6周以上。
结论: 小鼠中D-半乳糖和铝联合应用是一个有效的非转基因阿尔茨海默病(Alzheimer’s disease, AD)模型, 可用于AD病理研究和相关治疗药物的评价。