title: Subcutaneous administration of liraglutide ameliorates learning and memory impairment by modulating tau hyperphosphorylation via the glycogen synthase kinase-3β pathway in an amyloid β protein induced alzheimer disease mouse model.
abstract: Type 2 diabetes mellitus is a risk factor for Alzheimer's disease (AD). The glucagon-like peptide-1 analog liraglutide, a novel long-lasting incretin hormone, has been used to treat type 2 diabetes mellitus. In addition, liraglutide has been shown to be neurotrophic and neuroprotective. Here, we investigated the effects of liraglutide on amyloid β protein (Aβ)-induced AD in mice and explored its mechanism of action. The results showed that subcutaneous administration of liraglutide (25nmol/day), once daily for 8 weeks, prevented memory impairments in the Y Maze and Morris Water Maze following Aβ1-42 intracerebroventricular injection, and alleviated the ultra-structural changes of pyramidal neurons and chemical synapses in the hippocampal CA1 region. Furthermore, liraglutide reduced Aβ1-42-induced tau phosphorylation via the protein kinase B and glycogen synthase kinase-3β pathways. Thus liraglutide may alleviate cognitive impairment in AD by at least decreasing the phosphorylation of tau.
authors.affiliation: Department of Endocrinology, Union Hospital, Fujian Institute of Endocrinology, The Union Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, People's Republic of China.
authors.forename: Liqin
authors.initials: L
authors.lastname: Qi
authors.affiliation: Department of Endocrinology, Union Hospital, Fujian Institute of Endocrinology, The Union Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, People's Republic of China.
authors.forename: Linfang
authors.initials: L
authors.lastname: Ke
authors.affiliation: Department of Endocrinology, Union Hospital, Fujian Institute of Endocrinology, The Union Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, People's Republic of China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, Union Hospital, Fujian Institute of Endocrinology, The Union Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, People's Republic of China.
authors.forename: Lianming
authors.initials: L
authors.lastname: Liao
authors.affiliation: Department of Endocrinology, Union Hospital, Fujian Institute of Endocrinology, The Union Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, People's Republic of China.
authors.forename: Sujie
authors.initials: S
authors.lastname: Ke
authors.affiliation: Department of Endocrinology, Union Hospital, Fujian Institute of Endocrinology, The Union Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, People's Republic of China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, Union Hospital, Fujian Institute of Endocrinology, The Union Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, People's Republic of China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Union Hospital, Fujian Institute of Endocrinology, The Union Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, People's Republic of China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Endocrinology, Union Hospital, Fujian Institute of Endocrinology, The Union Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Endocrinology, Union Hospital, Fujian Institute of Endocrinology, The Union Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, People's Republic of China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, College of Pharmacy, Fujian Medical University, Fuzhou, Fujian, People's Republic of China. Electronic address: kellandchen1007@hotmail.com.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Endocrinology, Union Hospital, Fujian Institute of Endocrinology, The Union Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, People's Republic of China. Electronic address: libin_liu1@yeah.net.
authors.forename: Libin
authors.initials: L
authors.lastname: Liu
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D000069450:Liraglutide / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000648:ultrastructure; D010446:Peptide Fragments / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D065853:Spatial Learning / Q000187:drug effects; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D000067757:Glucagon-Like Peptide-1 Receptor; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D000069450:Liraglutide; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt
keywords: Alzheimer disease; Amyloid beta protein; GLP-1; GSK-3β; Tau protein