S-015 | Pathologically remodeled reactive astrocytes in an Alzheimer’s Disease (AD) Model

Cellular and Molecular Neurobiology
Author: Ingrid Eleonora Mailing | Email: mailingingridlabramos@gmail.com

Ingrid Mailing^1°4°, Ândria Cunha-Custódio^1°, Alicia Rossi^1°3°,  Dante Gómez Cuautle^1°, Sonia Do Carmo^2°, Claudio Cuello^2°, Diana Jerusalinsky^1°,  A. Javier Ramos^1°

^1° IBCN UBA-CONICET, School of Medicine, UBA, Argentina
^2° Dept Pharmacology and Therapeutics, McGill University, Montreal, Canada
^3° First Academic Unit of Histology, Embryology, Cell Biology and Genetics, School of Medicine, UBA, Argentina
^4° Chair of Neurophysiology, School of Psychology, UBA, Argentina

Astroglial alterations have been reported in various neurological disorders, including Alzheimer’s disease (AD). Specifically, astroglial atrophy has been observed in aged AD models and human samples. However, the specific timeline of astroglial dysfunction in AD remains incompletely understood. In this study, we used male and female McGill-R-Thy1-APP rats, which express the beta-amyloid precursor protein (AbetaPP) with Swedish and Indiana mutations, to investigate astroglial morphology, expression of homeostatic proteins, and markers of neurotoxic astrocytes at 7, 13, and 20 months of age (mo). Amyloid-beta (Aβ) plaques form very early in homozygous transgenic rats (7mo) and persist in older animals (13 and 20mo). Our results revealed morphological alterations in astrocytes in the proximity to Aβ plaques observed in 13mo male transgenic rats and to a lesser extent in females at 13 and 20mo. Sholl analysis identified three distinct astroglial cell phenotypes. The expression of astroglial homeostatic proteins, such as aquaporin 4 (AQP4) and glutamine synthetase (GS) showed a gradient of reduction towards the plaque. Interestingly, the neurotoxic astrocytic marker MAFG did not exhibit a similar gradient in transgenic rats. These findings provide preliminary evidence of pathological astroglial remodeling occurring in the early stages of Aβ plaque formation, preceding astroglial atrophy. This work was supported by PUE2018, UBACYT, PICT 2019-0851/2021-0760.