Early temporal short-term memory deficits in double transgenic APP/PS1 mice.
We tested single APP (Tg2576) transgenic, PS1 (PS1dE9) transgenic, and double APP/PS1 transgenic mice at 3 and 6 months of age on the acquisition of a hippocampal-dependent operant "differential reinforcement of low rate schedule" (DRL) paradigm. In this task mice are required to wait for at least 10 seconds (DRL-10s) between 2 consecutive nose poke responses. Our data showed that while single APP and PS1 transgene expression did not affect DRL learning and performance, mice expressing double APP/PS1 transgenes were impaired in the acquisition of DRL-10s at 6 months, but not at 3 months of age. The same impaired double transgenic mice, however, were perfectly capable of normal acquisition of signaled DRL-10s (SDRL-10s) task, a hippocampal-independent task, wherein mice were required to emit responses when the end of the 10-second delay was signaled by a lighting of the chamber. The age-dependent and early deficits of APP/PS1 mice suggest that the appetitive DRL paradigm is sensitive to the amyloid pathology present in double APP/PS1 mice, and that this mouse line represents a good model with which to study the efficacy of therapeutic strategies against Alzheimer's disease.
Lagadec
Saioa
S
CNIC, CNRS UMR 5228, Université Bordeaux 1, France.
Rotureau
Lolita
L
Hémar
Agnès
A
Macrez
Nathalie
N
Delcasso
Sebastien
S
Jeantet
Yannick
Y
Cho
Yoon H
YH
D000375:Aging / Q000235:genetics* / Q000523:psychology*; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal; D003216:Conditioning, Operant; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008570:Memory, Short-Term / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics*; D053764:Presenilin-1 / Q000235:genetics*; D011930:Reaction Time; D012055:Reinforcement Schedule; D019076:Transgenes / Q000235:genetics
C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1