Tau-knockout mice show reduced GSK3-induced hippocampal degeneration and learning deficits.

Abstract

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.

• Authors: Elena Gómez de Barreda, Mar Pérez, Pilar Gómez Ramos, Javier de Cristobal, Patricia Martín-Maestro, Asunción Morán, Hana N Dawson, Michael P Vitek, José J Lucas, Félix Hernández, Jesús Avila
• Journal: Neurobiology of disease (Neurobiol Dis) Vol. 37 Issue 3 Pg. 622-9 (Mar 2010) ISSN: 1095-953X [Electronic] United States
• PMID: 20004245 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: 2009 Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers
• beta Catenin
• tau Proteins
• Glycogen Synthase Kinase 3 beta
• Gsk3b protein, mouse
• Glycogen Synthase Kinase 3

Topics

• Alzheimer Disease (genetics, metabolism, physiopathology)
• Animals
• Atrophy (genetics, metabolism, pathology)
• Biomarkers (metabolism)
• Cell Nucleus (metabolism, pathology)
• Dentate Gyrus (metabolism, pathology, physiopathology)
• Disease Models, Animal
• Down-Regulation (genetics)
• Gene Expression Regulation, Enzymologic (genetics)
• Gliosis (genetics, metabolism, pathology)
• Glycogen Synthase Kinase 3 (genetics, metabolism)
• Glycogen Synthase Kinase 3 beta
• Hippocampus (metabolism, pathology, physiopathology)
• Learning Disabilities (genetics, metabolism, physiopathology)
• Maze Learning (physiology)
• Mice
• Mice, Knockout
• Mice, Transgenic
• Nerve Degeneration (genetics, metabolism, pathology)
• Neurofibrillary Tangles (genetics, metabolism, pathology)
• Neurons (metabolism, pathology)
• Phosphorylation
• beta Catenin (metabolism)
• tau Proteins (genetics, metabolism)