Early Impairments in Learning and Memory of the McGill-R-Thy1-APP transgenic rat model of AD

ACUTAIN, M. FLORENCIA; CERCATO, MAGALI C; DE TOMAS LIORO, ANNA; GONZALES GARELLO, TOMAS; CANAL, PILAR; KORNISIUK, EDGAR E; CUELLO, CLAUDIO; BAEZ, MARÍA VERÓNICA; JERUSALINSKY, DIANA ALICIA

CABA

Simposio; AAIC Satellite symposium; 2018

The McGill-R-Thy1-APP Tg rat (Leon et al. 2010), at variance with mostmouse transgenic (Tg) models, has a minimal genetic burden, as it carries asingle transgene. The expression of a modified variant of human APP751containing both the Swedish and Indiana mutations, leads to slow-progressingamyloid pathology associated with cognitive impairments. In homozygous (Ho) Tgrats, human Aβ accumulates intra-neuronally from one week postnatal and develops intoextracellular amyloid pathology by 6-9 months of age. On the other hand,McGill-R-Thy1-APP hemizygous (He) rats do not develop extracellular plaqueseven in 20 months old animals. Therefore, this Tg rat model offers a singular opportunity for testinglearning and memory abilities at early AD stages. He and Ho young adultMcGill-R-Thy1-APP Tg rats have been characterized in different behavioral taskand long term memory (LTM) was assessed only in the MWM task. In this paradigm,He and Ho rats exhibit different performances at different ages. For thisreason, in searching what are the earliest deficits in LTM acquisition and consolidationin this animal model, we decided to  analyze He rats performance atdifferent ages, compared with their wild type littermates in various tasks, ashabituation to an OF, inhibitory avoidance to a mild foot-shock, new objectlocation and new object recognition.