Donepezil improves the cognitive impairment in a tree shrew model of Alzheimer’s disease induced by amyloid-β1–40 via activating the BDNF/TrkB signal pathway
- 131 Downloads
Alzheimer’s disease (AD) is a chronic neurodegenerative disorder which can contribute to memory loss and cognitive damage in the elderly; moreover, evidence from clinical and animal studies demonstrated that AD always exhibit severe cognitive deficits. However, the effects of donepezil medications on cognition are controversial. Additionally, it is unclear whether donepezil can protect neurons to improve cognitive function through the brain-derived neurotropic factor (BDNF)/tyrosine receptor kinase B (TrkB) signalling pathway in the tree shrew (TS), which has a closer evolutionary relationship to primates than rodents. Here, we designed a study on an amyloid-β1–40 (Aβ1–40)-induced TS model of AD and investigated the molecular mechanism by which donepezil protects neurons and improves cognitive function through activating the BDNF/TrkB signalling pathway. The results showed that donepezil could rescue Aβ1–40-induced spatial cognition deficits, and reverse Aβ1–40-induced temporal horn along with ADC enlargement in the TS brain. Meanwhile, it suppressed Aβ1–40-induced neuronal damage and loss of body weight. Intriguingly, donepezil could increase the choline acetyl transferase (ChAT) expression level and reduce the fibrillary acid protein (GFAP) expression level in the hippocampus and cortex of TS. Additionally, donepezil significantly upregulated the expression level of BDNF, as well as the phosphorylated level of TrkB. These results suggested that donepezil could protect neurocytes from senility and ameliorate learning and memory impairment in the TS model of AD, which appeared to be through regulating the cholinergic system and inhibiting the BDNF/TrkB-dependent signalling pathway. Moreover, the study underlines the potency of TS to be a novel animal model for research on AD, and it deserves intensive attention.
KeywordsAlzheimer’s disease Tree shrews Cognitive function BDNF/TrkB signalling Donepezil
This study was supported by grants from the National Natural Science Foundation of China (81460647) and the CAMS Initiative for Innovative Medicine (2016-I2M-2-006).
Compliance with ethical standards
Conflict of interest
The authors report no conflicts of interest in this work.
- Darocha-Souto B, Scotton TC, Coma M, Serrano-Pozo A, Hashimoto T, Serenó L, Rodríguez M, Sánchez B, Hyman BT, Gómez-Isla T (2011) Brain oligomeric β-amyloid but not total amyloid plaque burden correlates with neuronal loss and astrocyte inflammatory response in amyloid precursor protein/tau transgenic mice. J Neuropathol Exp Neurol 70:360–376CrossRefGoogle Scholar
- Sampedro-Piquero P, Moreno-Fernández RD, Mañas-Padilla MC, Gil-Rodríguez S, Gavito AL, Pavón FJ, Pedraza C, García-Fernández M, Guevara-Miranda DLD, Santín LJ (2018) Training memory without aversion: appetitive hole-board spatial learning increases adult hippocampal neurogenesis. Neurobiol Learn Mem 151:35–42CrossRefGoogle Scholar
- Shujiang S, Cong W, Chengbing G, Xu H, Liecheng W, Chen Z (2015) The formation and extinction of fear memory in tree shrews. Front Behav Neurosci 9:204Google Scholar
- Wang YL, Kuang DX, Zhao-Xia MA, Wang YJ, Zhang LD, Gao B, Xian-Xin XU, Min HU, Duan YQ, G. M. University (2015) Establishment of an osteoporosis model in tree shrews by bilateral ovariectomy. Acta Laboratorium Animalis Scientia Sinica 23:562–66Google Scholar
- Xu L, Chen SY, Nie WH, Jiang XL, Yao YG (2012) Evaluating the phylogenetic position of Chinese tree shrew (Tupaia belangeri chinensis) based on complete mitochondrial genome: implication for using tree shrew as an alternative experimental animal to primates in biomedical research. J Genet Genomics 39:131–137CrossRefGoogle Scholar