Alzheimer-associated mutant ubiquitin impairs spatial reference memory
| Autor: | Paula van Tijn, Melly S. Oitzl, David F. Fischer, Marian C. Verhage, Barbara Hobo, Fred W. van Leeuwen |
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| Přispěvatelé: | Netherlands Institute for Neuroscience (NIN), Psychiatrie & Neuropsychologie, RS: MHeNs School for Mental Health and Neuroscience |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Male
Genetically modified mouse Proteasome Endopeptidase Complex Spatial Behavior Mice Transgenic Experimental and Cognitive Psychology Motor Activity Transgenic mouse model Mice Behavioral Neuroscience Prosencephalon Degenerative disease Ubiquitin medicine Animals Humans Neurodegeneration Maze Learning Neurologic Examination Analysis of Variance Memory Disorders Behavior biology Age Factors medicine.disease Motor coordination Mice Inbred C57BL Mutant ubiquitin Disease Models Animal Gene Expression Regulation Proteasome Rotarod Performance Test Ubiquitin-proteasome system Mutation Forebrain biology.protein Alzheimer's disease Neuroscience Psychomotor Performance |
| Zdroj: | Physiology & Behavior, 102, 193-200. Elsevier B.V. Physiology & Behavior, 102(2), 193-200. Elsevier Science |
| ISSN: | 0031-9384 |
| DOI: | 10.1016/j.physbeh.2010.11.001 |
| Popis: | UBB + 1 is a mutant ubiquitin which accumulates in the hallmarks of tauopathies, including Alzheimer's disease. Transgenic mice expressing high levels of neuronal UBB + 1 exhibit moderately decreased proteasome activity and spatial reference memory deficits at 9 months of age. In the present study, we characterized the behavioral phenotype of male UBB + 1 transgenic mice at different ages. We show that UBB + 1 transgenic mice displayed an age-related functional decline similar to wild-type littermates, without gross neurological abnormalities or alterations in procedural motor-learning and motor coordination. At 15 months of age, a transgene-specific spatial learning deficit was dependent on the period of training in the Morris watermaze. This deficit could be eliminated after additional training. We conclude that the previously reported spatial reference memory deficits of UBB + 1 transgenic mice persist during aging. In addition, our results demonstrate that the subtle defect in spatial reference memory formation, caused by a decrease in forebrain proteasome activity, is a persistent defect and not a structural defect. |
| Databáze: | OpenAIRE |
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