1 Department of Pharmacology, School of Medicine, Jinan University, Guangzhou 510632, China
2 Institute of Brain Science, Jinan University, Guangzhou 510632, China
3 Joint Laboratory for Brain Function and Health, Jinan University and The University of Hong Kong, Jinan University, Guangzhou 510632, China

Abstract 

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.

Keywords

Alzheimer’s disease; brain change; D-galactose; aluminum; neurodegenerative disease; animal model

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