033 | Characterization of reactive astrocytes and peri-plaque astrocytes in an Alzheimer’s Disease (AD) rat model

Cellular and Molecular Neurobiology

Author: Ingrid Eleonora Mailing | Email: mailingingridlabramos@gmail.com

Ingrid Mailing 1°4°, Alicia Rossi 1°3°, Dante Gomez Cuautle , Melissa Yael Bromberg , Martín Habif , Sonia Do Carmo , A. Claudio Cuello , Diana Jerusalinsky , A. Javier Ramos

1° IBCN UBA-CONICET, Facultad de Medicina, UBA, Argentina
2° Dept Pharmacology and Therapeutics, McGill University, Montreal, Canadá
3° Primera UA de Histología, Embriología, Biología Celular y Genética, Facultad de Medicina, UBA, Argentina
4° Cátedra de Neurofisiología, Facultad de Psicología, UBA, Argentina.

Astrocytes are essential for the maintenance of the brain homeostasis. In AD it has been proposed that astrocytes may suffer an atrophy that reduces their ability to sustain neuronal metabolism and synaptic function. We here analyzed in detail the astroglial morphology, the expression of essential astroglial proteins glutamine synthase (GS) and aquaporin-4 (AQP4), the rate of neuronal survival and the presence of A? plaques in the brain cortex. Employing the McGill-R-Thy1-APP transgenic rat (Tg) model of AD at 7, 13, and 20 months of age, we compared heterozygous, homozygous and wild-type animals. We observed that plaques are present in homozygous animals at 13 and 20 months and GFAP+ reactive astrocytes are morphologically different at different distances of the plaque by Sholl analysis. Reactive astrogliosis was already observed in 7 months-old Tg animals, at the pre-plaque stage. At 13 months, a reduction in GS expression was evident in peri-plaque astrocytes, while distal astrocytes remained unaffected. The typical end-feet AQP4 expression was lost in peri-plaque astrocytes. The abundance of cortical neurons declines from 7 to 20 months in both wild type and Tg rats.
Our findings indicate that reactive astrogliosis precedes plaque formation and occurs in absence of significant neuronal loss. In addition, astrocytic homeostatic ability declines in the proximity to the plaques presenting atypical morphologies compared with distal astrocytes.