Cognitive impairment and reactive gliosis in a rat model of AD-like brain amyloidosis

CATERINA SISTER; MARTIN HABIF; FEDERICO FILIPPIN ; ALICIA ROSSI; VALERIA BERCOWICZ; A. CLAUDIO CUELLO; ALBERTO JAVIER RAMOS; DIANA JERUSALINSKY

Modalidad Virtual

Congreso; XXXV Reunión anual SAN 2020; 2020

SAN

Alzheimer´s disease (AD) is a progressive neurodegenerative disorder with overproduction of Aβ peptides in the brain that ultimately aggregate into insoluble fibrils forming plaques, inducing a sustained inflammatory response known as ?reactive gliosis?. Previous reports using mice AD models pointed out some glial cell alterations.McGill-Thy1-APP transgenic (Tg) rat model of AD-like brain amyloidosis reliably resembles human neural and cognitive disease development. We have addressed the influence of sexual dimorphism in learning and memory, showing deficits in long-term associative memory (spatial and aversive) in 13 month-old heterozygous males. Hence, we performed an imaging-based quantitative study to gain insight into Aβ deposition and reactive gliosis in those Tg rats and their wild type littermates (wt). Analysis of Tg rat brain slices showed Aβ deposition in plaques, preferentially localized in hippocampus and somatosensory cortex and an increased GFAP+ area. By using morphological descriptors, we analyzed cell size and shape to determine the degree of reactive gliosis in rats of both genotypes. Astrocytes in Tg animals were bigger, extensively branched, likely consistent with an exacerbated inflammatory response, compared with a smaller area and perimeter, more ameboid-shaped/poorly ramified astrocytes in wt rats. These results point to the relevance of searching for an interplay between reactive gliosis and mild cognitive impairment at middle age.