123 + CO-4-Microcine | Streptozotocin induces behavioral changes and reactive astrocytes in a sex-dependent manner

Cognition, Behavior, and Memory

Author: Juliette López Hanotte | Email: julietteloha@gmail.com

Juliette López Hanotte , Facundo Peralta , María Angeles Carrillo-de Sauvage , Carole Escartin , Paula Cecilia Reggiani

1° Universidad Nacional de La Plata, Instituto de Investigaciones Bioquímicas de La Plata, Argentina.
2° Université Paris-Saclay, CEA, CNRS, Laboratoire des Maladies Neurodégénératives, Fontenay-aux-Roses, France

Male rodents have been the default model organism in neuroscience research, including for the intracerebroventricular (icv) streptozotocin (STZ)-induced Alzheimer’s disease (AD) model. Our objective was to compare the effect of icv-STZ injection in male and female rats with and without ovaries. Male rats were separated into control and STZ groups. Fourteen days before STZ injection, half of female rats were ovariectomized (OVX), or left with intact ovaries (Female group), and then separated into control or STZ groups on the same day as male rats. Two weeks later, behavioral tests were conducted for spatial memory (Barnes Maze) and depressive-like behavior (Forced swimming test). Immunofluorescence analyses were performed in the hippocampus. STZ affected spatial memory and increased depressive behavior in male, but not in female rats. We assessed GFAP expression and JAK2/STAT3 signaling activation, and we found sex differences on astrocyte reaction to STZ, with astrocyte reactivity evidence only in male rats. Also, STZ induced synapse loss in male rats, although it did not affect the expression of astrocyte proteins relevant for synapses, independent of the sex. We conclude that STZ affected differentially male and female rats, and OVX did not render the rats more vulnerable to STZ. Therefore, experimental design changes should be considered in order to set up a female sporadic AD model, and sex differences in the icv-STZ model should be addressed and further studied.