Sex dependent correlation of spleen atrophy and behavior deficits induced by binge treatment with ethanol in rodent models.

Abstract

Objectives: During physical and psychosocial development, many adolescents engage in binge alcohol drinking. Ethanol (EtOH) is the key chemical in alcoholic beverages. EtOH intoxication impairs locomotor behaviors. We previously found that binge treatment with EtOH (BE) causes spleen atrophy, leading to immune dysregulation. With these premises, we hypothesized that BE-induced spleen atrophy is correlated with compromised locomotion and behaviors in adolescence.

Methods: We exposed F344 rats to either 3 days of BE (mimicking college drinking) or water following pubertal onset. 24 h following the last BE, we assessed behaviors using ANY-Maze, focusing on locomotor activity, freezing, and thigmotaxis, before spleen collection. Correlation analysis and Linear Regression analysis quantified BE's effects on behavior. In parallel, we used GEO2R to obtain differentially expressed genes (DEGs) from public dataset GSE49028 (B6129Sf2/J mice were given BE) and identified signaling pathways in the prefrontal cortex (PFC) involved in BE compromising locomotion and increasing anxiety.

Results: BE significantly decreased spleen size. Interestingly, we found that BE exposure had a gender-dependent impact, affecting males more than females. Furthermore, functional analysis of the dataset identified several targets of interest including the downregulation of BDNF as a critical regulator of behavioral deficit following BE treatment.

Conclusions: Using data-driven discovery and hypothesis-testing investigation to integrate these two studies, we provide an understanding of the underlying biological mechanism of BE-induced spleen atrophy-associated behavioral impairments through the genetic alterations in the PFC. Our findings will help develop a potent, powerful cocktail of reagents to treat behavioral impairment in those who binge drink.