Tauroursodeoxycholic acid (TUDCA) supplementation prevents cognitive impairment and amyloid deposition in APP/PS1 mice

Neurobiology of Disease

Rudi D'Hooge¹  Adrian C. Lo²  Zsuzsanna Callaerts-Vegh²  Ana F. Nunes³  Cecília M.P. Rodrigues³ 

[1] Department of Biochemistry and Human Biology, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal;Laboratory of Biological Psychology, Faculty of Psychology and Educational Sciences, University of Leuven, Leuven, Belgium;Research Institute for Medicines and Pharmaceutical Sciences, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal;

关键词: Alzheimer's disease;    APP/PS1;    TUDCA;    Learning and memory;    Morris water maze;   

DOI  :  

来源: DOAJ

【 摘 要 】

Alzheimer's disease (AD) is a neurodegenerative disease hallmarked by extracellular Aβ1–42 containing plaques, and intracellular neurofibrillary tangles (NFT) containing hyperphosphorylated tau protein. Progressively, memory deficits and cognitive disabilities start to occur as these hallmarks affect hippocampus and frontal cortex, regions highly involved in memory. Connective tissue growth factor (CTGF) expression, which is high in the vicinity of Aβ plaques and NFTs, was found to influence γ-secretase activity, the molecular crux in Aβ1–42 production. Tauroursodeoxycholic acid (TUDCA) is an endogenous bile acid that downregulates CTGF expression in hepatocytes and has been shown to possess therapeutic efficacy in neurodegenerative models. To investigate the possible in vivo therapeutic effects of TUDCA, we provided 0.4% TUDCA-supplemented food to APP/PS1 mice, a well-established AD mouse model. Six months of TUDCA supplementation prevented the spatial, recognition and contextual memory defects observed in APP/PS1 mice at 8 months of age. Furthermore, TUDCA-supplemented APP/PS1 mice displayed reduced hippocampal and prefrontal amyloid deposition. These effects of TUDCA supplementation suggest a novel mechanistic route for Alzheimer therapeutics.

【 授权许可】

Unknown