Tau-knockout mice show reduced GSK3-induced hippocampal degeneration and learning deficits.
It has been proposed that deregulation of neuronal glycogen synthase kinase 3 (GSK3) activity may be a key feature in Alzheimer disease pathogenesis. We have previously generated transgenic mice that overexpress GSK3beta in forebrain regions including dentate gyrus (DG), a region involved in learning and memory acquisition. We have found that GSK3 overexpression results in DG degeneration. To test whether tau protein modified by GSK3 plays a role in that neurodegeneration, we have brought GSK3 overexpressing mice to a tau knockout background. Our results indicate that the toxic effect of GSK3 overexpression is milder and slower in the absence of tau. Thus, we suggest that the hyperphosphorylated tau mediates, at least in part, the pathology observed in the brain of GSK3 overexpressing mice.
Gómez de Barreda
Elena
E
Centro de Biología Molecular Severo Ochoa, C/Nicolás Cabrera, 1. Universidad Autónoma de Madrid, Campus Cantoblanco. 28049 Madrid, Spain.
Pérez
Mar
M
Gómez Ramos
Pilar
P
de Cristobal
Javier
J
Martín-Maestro
Patricia
P
Morán
Asunción
A
Dawson
Hana N
HN
Vitek
Michael P
MP
Lucas
José J
JJ
Hernández
Félix
F
Avila
Jesús
J
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D001284:Atrophy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D018891:Dentate Gyrus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D005911:Gliosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007859:Learning Disabilities / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016874:Neurofibrillary Tangles / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D051176:beta Catenin / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
D015415:Biomarkers; D051176:beta Catenin; D016875:tau Proteins; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3