Perinatal exposure to ethanol and gestational environmental enrichment in mice: Study of synaptic proteins and inflammatory response associated with learning and memory

• Grant number: 24/23031-3
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: October 01, 2025
• End date: July 31, 2028
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Rosana Camarini
• Grantee: Maylin Hanampa Maquera
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 23/13110-0 - The Influence of Ethanol on Maternal Behavior and Offspring: Exploring the Behavioral and Neural Protective Mechanisms of Environmental Enrichment, AP.R

Abstract

Perinatal exposure to ethanol (PEE), in both humans and rodents, significantly impairs the offspring's central nervous system. Due to the high plasticity of the brain, external factors such as ethanol can trigger neuroinflammation and disrupt synaptic connections, resulting in deficits in learning and memory. Despite the importance of this issue, available treatments and preventive strategies for the effects of PEE remain insufficient. Environmental enrichment (EE) has emerged as a promising approach for modulating the adverse effects of various neuropsychiatric and neurodegenerative conditions. EE involves exposure to physically, socially, and cognitively stimulating environments, which can enhance brain plasticity, induce the expression of synaptic proteins, and reduce neuroinflammatory processes. This intervention has demonstrated benefits in improving cognitive functions, including memory and learning, and may represent an effective strategy to mitigate the damage associated with PEE. This study aims to investigate the potential of EE during pregnancy as an intervention to counteract the harm caused by ethanol exposure. We will assess changes in gene and protein expression of synaptic proteins and neuroinflammation-associated molecules related to memory and learning processes in the prefrontal cortex (PFC) and hippocampus (HPC) of the offspring and dams. To this end, pregnant Swiss mice will be allocated into four experimental groups: (1) standard cage housing with water treatment (CT), (2) standard cage housing with ethanol treatment (ETOH), (3) EE housing for 3 hours/day with water treatment (EE-CT), and (4) EE housing for 3 hours/day with ethanol treatment (EE-ETOH). Ethanol (3 g/kg) or water treatment will be administered from gestational day 15 (GD15) to postnatal day 10 (PND10), corresponding to the third trimester of human pregnancy. Synaptic protein and neuroinflammatory molecule expression will be analyzed on PND11, a period of high vulnerability in neurodevelopment. Offspring behaviors will be assessed during adolescence, focusing on memory and learning, to determine the persistence of changes over development. This study seeks to provide new evidence on the role of gestational EE in preventing PEE-induced damage, contributing to the development of more effective therapeutic strategies.