MEMORY DEFICITS AND PLASTICITY GENES IN A RAT MODEL OF ALZHEIMER DISEASE

DIANA JERUSALINSKY; SONIA DO CARMO; VERONICA BAEZ; VALERIA BERCOWICZ; CATERINA SISTER; CLAUDIO CUELLO

Montreal

Encuentro; ISN-ASN; 2019

ISN-ASN

McGill-R-Thy1-APP Wistar-transgenic (Tg) rats, bearing human amyloid precursorprotein with Swedish and Indiana mutations of familial Alzheimer´s disease (AD), are suitable for testing learning and memory at AD onset. Three month old (mo) Homozygous Tg rats show cognition deficits; human amyloid-β (Aβ) accumulates from first week, developing extra cellular amyloid pathology in 6-9 mo animals. Hemizygous Tg (He) does not develop extra cellular plaques even at 20 months. Three, 4 and 6 mo He male rats and their wild-type litter-mates (WT) explored an open field (OF) for 5min. When tested 24h later (long-term-memory, LTM), denoted habituation to the environment. Same He and WT rats were trained for object recognition (OR) and inhibitory avoidance (IA) of a mild foot-shock. All groups discriminated new versus known object 1h later (short-term-memory), but 4 and 6 mo He did not show OR-LTM neither IA-LTM. Then, some plasticity genes were investigated in 4mo He rats. There were no significant differences for PSD95, Arc, GluR1 AMPA receptor or NR1- and NR2A-NMDA receptor subunits; though NR2B and CaMKIIb mRNAs levels were significantly higher at the hippo campus, suggesting an expression in crease. These results strongly suggest that deficits in certain LTM de velop s from 4 months. Further investigation is necessary to interpre the hippocampal CaMKIIb and NR2B mRNAs in crease, which could be due to intracellular Ca2+ rise following overstimulation by Aβ/Aβ oligomers.