Rat Model of Late Gestational Alcohol Exposure Produces Similar Life-Long Changes in Thalamic Nucleus Reuniens Following Moderate- Versus High-Dose Insult.

Abstract

Recent studies have recognized that thalamic nucleus reuniens (Re) undergoes substantial neuron loss following alcohol exposure (AE) during the brain growth spurt (BGS). As all previous studies have utilized high-dose AE paradigms, we tested whether moderate-dose AE is capable of damaging Re to a similar degree as high-dose AE. We used a rat model of third-trimester binge AE (relative to human pregnancy) to administer ethanol to rat pups at either a high (5.25g/kg/day) or moderate (3.00g/kg/day) dose during the BGS (postnatal days [PD] 4-9) via intragastric intubation. In adulthood (i.e. PD72), we quantified the volume of Re as well as the total number of neurons and non-neuronal cells in the nucleus (which were further divided into microglia versus 'other' non-neurons), using unbiased stereological estimation of cells identified with immunofluorescent markers (i.e. nuclear label Hoechst, neuron-specific protein NeuN, and microglia-specific protein Iba1). Data were analyzed both between-treatment and correlated with peak blood alcohol concentration (BAC). We observed significant neuronal and non-neuronal cell loss in both the high-dose and moderate-dose AE groups (relative to both procedural control and typically-developing control groups), which mediated reductions in Re volume. Outcomes did not correlate with peak BAC, further supporting that Re is vulnerable to AE-induced neurodegeneration at lower doses than previously suspected. Given the role that Re has in coordinating prefrontal cortex and hippocampus, the current study highlights the role that thalamic damage may play in the range of behavioral alterations observed in Fetal Alcohol Spectrum Disorders.