title: Hyperphosphorylation of Tau at Ser396 occurs in the much earlier stage than appearance of learning and memory disorders in 5XFAD mice.
abstract: The present study investigated the relation of age-dependent spatial learning/memory impairment and Tau phosphorylation in 5XFAD mice, a model of Alzheimer's disease. In the water maze test, the acquisition and retention latencies for 5XFAD mice at 6 months, but not 2 months, of age was significantly longer than those for wild-type mice at the same months of age, without difference in the swim speed and visual acuity between two groups. The level of glycogen synthase kinase 3β (GSK-3β) phosphorylation at Ser9 in the hippocampus for the 5XFAD mice at >4 months of age was significantly lesser than that for wild-type mice at the same months of age, while a robust increase in the Tyr216 phosphorylation of GSK-3β was found both in wild-type and 5XFAD mice at 6 months of age, without no significant difference in the extent between two groups. There was no significant difference in the Tau phosphorylation at Ser202/Thr205 in the hippocampus between two groups, but Ser396 phosphorylation for 5XFAD mice was significantly higher than that for wild-type mice at ages ranging from 2 to 6 months. The results of the present study indicate that Tau hyperphosphorylation in the brain for 5XFAD mice precedes high activation of GSK-3β and occurs in the much earlier stage than appearance of learning and memory disorders.
authors.affiliation: Division of Bioinformation, Department of Physiology, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kanno
authors.affiliation: Division of Bioinformation, Department of Physiology, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Tsuchiya
authors.affiliation: Division of Bioinformation, Department of Physiology, Hyogo College of Medicine, Nishinomiya, Japan. Electronic address: tomoyuki@hyo-med.ac.jp.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Nishizaki
mesh_terms: D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D007859:Learning Disabilities / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D018782:Maze Learning; D008569:Memory Disorders / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010766:Phosphorylation / Q000235:genetics; D053764:Presenilin-1 / Q000235:genetics; D011930:Reaction Time / Q000235:genetics; D012694:Serine / Q000378:metabolism*; D013550:Swimming; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016564:Amyloid beta-Protein Precursor; C508853:PSEN1 protein, human; D053764:Presenilin-1; D016875:tau Proteins; D012694:Serine; D038362:Glycogen Synthase Kinase 3
keywords: 5XFAD mouse; GSK-3β; Spatial learning and memory; Tau; Water maze test