D-068 | Gene Therapy with Insulin-like Growth Factor 1 in Hippocampal Astrocytes of Aged Rats

Cognition, Behavior, and Memory
Author: Ana Abril Vidal Escobedo | Email: avidalescobedo@med.unlp.edu.ar

Ana Abril Vidal Escobedo^1°, Facundo Peralta^1°, Julia Emilia Alejandra Díaz Baliero^1°,  Candela Mutuberría^1°, Joaquín Pardo^1°, Paula Cecilia Reggiani^1°

^1° Instituto de Investigaciones Bioquímicas de La Plata `Prof. Dr. Rodolfo R. Brenner´ (CONICET-UNLP)

Aging is associated with numerous anatomical, physiological and gene expression alterations in the hippocampus, a key structure for memory. In this region, astrocytes are fewer, smaller, and have shorter and sparser branches. We hypothesize that overexpression of Insulin-like Growth Factor 1 (IGF1) in hippocampal astrocytes of aged rats will modulate their trophic functions, leading to positive effects on behavior. Previously, we analyzed astrocyte arborization in 2-month-old male Sprague-Dawley (SD) rats transduced with a bicistronic adeno-associated virus (AAV) overexpressing IGF1 or GFP (a control vector expressing green fluorescent protein), followed by red fluorescent protein tdTomato (a marker gene for visualizing transduced cells) under an astrocyte-specific promoter. Morphometric analysis of astrocytes from AAV-IGF1-injected rats showed significant increases in arborization and extension length compared to controls. With this system, we aim to evaluate if IGF1 overexpression in astrocytes improves behavior in aged rats. Female SD rats aged 20 months were used, divided into Intact and IGF1 groups. Six weeks before sacrifice, behavioral tests to assess species-typical, exploratory, anxiety-like, depressive-like behaviors, and recognition memory were performed. Preliminary results indicated that aged rats treated with AAV-IGF1 improved its behavior and cognitive performance. Thus, IGF1 overexpression in astrocytes improved certain deteriorated behaviors in aged rats.