Alzheimer-associated mutant ubiquitin impairs spatial reference memory.
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.
Netherlands Institute for Neuroscience, an institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.
Paula
P
van Tijn
Barbara
B
Hobo
Marian C
MC
Verhage
Melly S
MS
Oitzl
Fred W
FW
van Leeuwen
David F
DF
Fischer
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D009460:Neurologic Examination; D016548:Prosencephalon / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011597:Psychomotor Performance / Q000502:physiology; D045442:Rotarod Performance Test; D013037:Spatial Behavior / Q000502:physiology*; D025801:Ubiquitin / Q000235:genetics* / Q000378:metabolism
C479419:UBB protein, human; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex