Do early life seizures disrupt the oxytocin system and pair bond formation in prairie voles (Microtus ochrogaster)?

• Grant number: 22/15753-3
• Support Opportunities: Scholarships abroad - Research
• Start date: August 25, 2023
• End date: February 24, 2024
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Roberta Monterazzo Cysneiros
• Grantee: Roberta Monterazzo Cysneiros
• Host Investigator: Larry James Young
• Host Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Presbiteriana Mackenzie (UPM). Instituto Presbiteriano Mackenzie. São Paulo , SP, Brazil
• Institution abroad: Emory University, United States

Abstract

Epilepsy is one of the most common neurological diseases, affecting over 70 million people worldwide. Growing evidence has shown that patients with temporal lobe epilepsy (TLE), frontal lobe epilepsy (FLE) and idiopathic epilepsies, even without the diagnosis of autism, present deficits in theory of mind (ToM) and in facial emotion recognition, especially for fear, which affect social affiliation and the quality of life. The neural mechanism underlying social dysfunction is poorly understood and there is a growing interest in addressing this issue in animal models. Neonatal seizures in rodents have been considered a promising model to study the mechanisms underlying social behavior impairment, as these animals present high-functioning autism-like phenotype, as chronic socialization abnormalities revealed by deficit in social play behavior, low social preference for novelty and deficit in social discrimination, elevated emotionality, impaired ultrasonic vocalization, and mild or no cognitive deficits, depending on the task demand. Previous results suggest that disruption in oxytocin signaling may be involved in the social deficits mentioned above. In this context, the socially monogamous prairie vole (Microtus ochrogaster) represents an excellent model for the investigation of the role of oxytocin in social behavior, especially social bonding. Here, we hypothesized that early life seizures disrupt the oxytocin system in prairie voles with subsequent impact on social behavior. The goal is to determine if early life seizures disrupt oxytocin system, contributing to later pair bonding impairment in prairie voles. For that, pair bonded young adult male voles subjected to saline or pilocarpine administration in neonatal period will be evaluated in partner preference tests in a three-chamber apparatus, following by Chromogenic RNAscope in situ hybridization for mapping oxytocin receptor (OTR) mRNA throughout the brain. (AU)