title: Liraglutide Improves Water Maze Learning and Memory Performance While Reduces Hyperphosphorylation of Tau and Neurofilaments in APP/PS1/Tau Triple Transgenic Mice.
abstract: The purpose of this study was to explore how liraglutide affects AD-like pathology and cognitive function in APP/PS1/Tau triple transgenic (3 × Tg) Alzheimer disease (AD) model mice. Male 3 × Tg mice and C57BL/6 J mice were treated for 8 weeks with liraglutide (300 μg/kg/day, subcutaneous injection) or saline. Levels of phosphorylated tau, neurofilaments (NFs), extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) in brain tissues were assessed with western blots. Fluoro-Jade-B labeling were applied to detect pathological changes. The Morris water maze (MWM) was used to assess the spatial learning and memory. Liraglutide decreased levels of hyperphosphorylated tau and NFs in 3 × Tg liraglutide-treated (Tg + LIR) mice, increased ERK phosphorylation, and decreased JNK phosphorylation. Liraglutide also decreased the number of degenerative neurons in the hippocampus and cortex of Tg + LIR mice, and shortened their escape latencies and increased their hidden platform crossings in the MWM task. Liraglutide did not significantly affect the animals' body weight (BW) or fasting blood glucose. Liraglutide can reduce hyperphosphorylation of tau and NFs and reduce neuronal degeneration, apparently through alterations in JNK and ERK signaling, which may be related to its positive effects on AD-like learning and memory impairment.
authors.affiliation: Pathophysiology Department, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
authors.forename: Shuyi
authors.initials: S
authors.lastname: Chen
authors.affiliation: Pathophysiology Department, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Pathology, Tianjin Cancer Hospital, Tianjin Medical University, Tianjin, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Pathophysiology Department, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
authors.forename: Ai
authors.initials: A
authors.lastname: Guo
authors.affiliation: Pathophysiology Department, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Food science and Biological Engineering Department, Tianjin Agriculture University, Tianjin, China.
authors.forename: Rongxia
authors.initials: R
authors.lastname: Fu
authors.affiliation: Pathophysiology Department, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. 1766464240@qq.com.|, No. 22, Qi Xiang Tai Road, He Ping District, Tianjin, China. 1766464240@qq.com.
authors.forename: Yanqiu
authors.initials: Y
authors.lastname: Deng
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007382:Intermediate Filaments / Q000187:drug effects / Q000378:metabolism*; D000069450:Liraglutide / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology*; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D053764:Presenilin-1 / Q000235:genetics; D011897:Random Allocation; D016875:tau Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D016564:Amyloid beta-Protein Precursor; D007004:Hypoglycemic Agents; D053764:Presenilin-1; D016875:tau Proteins; D000069450:Liraglutide
keywords: 3 × Tg mice; Alzheimer disease; ERK; JNK; Liraglutide; Tau