79. Does moderate in utero alcohol exposure result in inflammation in the developing brain?

Abstract

Alcohol exposure during early fetal development can have significant consequences for neural development and function. To determine whether moderate alcohol exposure in early pregnancy can induce pro-inflammatory cytokine and chemokine expression in the fetal brain, pregnant Sprague–Dawley rats were treated with alcohol or water from embryonic days (E) 10 to 16. This treatment regimen (50% ethanol 2X/day) produced a daily blood alcohol concentration of 0.08% for ∼8 h. On E17, the hippocampus-cortex of each pup was collected for the analysis of pro-inflammatory cytokines and chemokines using real-time PCR. Alcohol exposure increased the expression of cytokines in the tumor necrosis factor superfamily, including TNF-α, TNF-SF13, and TNF-SF13B in females but not males. CCL2 and CCL20 revealed opposing expression trends in males and females such that levels decreased in males and increased in females following alcohol treatment. We also found a significant increase in IL-6 and TNF-SF4 in the placenta of both males and females exposed to moderate fetal alcohol levels. In a second experiment, we repeated the experimental paradigm and raised pups to adulthood to measure cytokines and chemokines following a mild lipopolysaccharide challenge. We predict that pups exposed to moderate prenatal alcohol may express a stronger neuroimmune or peripheral immune response to this challenge in adulthood. Future experiments will investigate potential behavioral or cognitive deficits brought on by mild prenatal ethanol exposure. Supported by 5P20GM103653-02.