Alzheimer-associated mutant ubiquitin impairs spatial reference memory.

Autor: van Tijn P; Netherlands Institute for Neuroscience, an institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands., Hobo B, Verhage MC, Oitzl MS, van Leeuwen FW, Fischer DF
Jazyk: angličtina
Zdroj: Physiology & behavior [Physiol Behav] 2011 Feb 01; Vol. 102 (2), pp. 193-200. Date of Electronic Publication: 2010 Nov 06.
DOI: 10.1016/j.physbeh.2010.11.001
Abstrakt: 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 9months 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 15months 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.
(Copyright © 2010 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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