Abstract

Microglia, the immune cells of the brain, are important and necessary for appropriate neural development; however, activation of microglia, concomitant with increased levels of secreted immune molecules during brain development, can leave the brain susceptible to certain long-term changes in immune function associated with neurological and developmental disorders. One mechanism by which microglia can be activated is via alcohol exposure. We sought to investigate if low levels of prenatal alcohol exposure can alter the neuroimmune response to a subsequent acute dose of alcohol in adulthood. We also used the novel object location and recognition memory tasks to determine whether there are cognitive deficits associated with low prenatal alcohol exposure and subsequent adulthood alcohol exposure. We found that adult rats exposed to an acute binge-like level of alcohol, regardless of gestational alcohol exposure, have a robust increase in the expression of Interleukin (IL)-6 within the brain, and a significant decrease in the expression of IL-1β and CD11b. Rats exposed to alcohol during gestation, adulthood, or at both time points exhibited impaired cognitive performance in the cognitive tasks. These results indicate that both low-level prenatal alcohol exposure and even acute alcohol exposure in adulthood can significantly impact neuroimmune and associated cognitive function.

Highlights

  • Microglia are the innate immune cells of the brain and have a critical role in maintaining brain homeostasis

  • Euthanasia, Perfusion, and Tissue Collection In Experiment 1, we examined the cytokine response in the brain produced by an acute dose of alcohol administered to adult rats that had been previously treated in utero with a low dose of fetal alcohol or water (n = 6–9 rats/group) in order to measure the function of microglia in response to these challenges

  • We found a main effect of sex (F1,50 = 6.273; p = 0.016), prenatal alcohol exposure (F1,50 = 8.971; p = 0.005), and adulthood alcohol treatment (F1,50 = 17.292; p < 0.001) on the expression levels of IL-1β (Figure 2A)

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Summary

Introduction

Microglia are the innate immune cells of the brain and have a critical role in maintaining brain homeostasis. Microglia survey and monitor their surroundings, engage in phagocytosis of dying neural cells, and prune or refine weak synaptic connections among other neurodevelopmental processes. Their importance in the brain becomes even more evident in the event of injury, infection, or other insult. In response to these adverse conditions, microglia change their morphology from ramified, quiescent cells to amoeboid, macrophage-like active cells that release cytokines and chemokines. Inappropriate microglial activation has been linked to a number of neurodevelopmental disorders, including schizophrenia and autism spectrum disorder [3,4,5], as well as later-life cognitive disorders like Alzheimer’s disease [6,7,8,9], alcoholism and alcohol related cognitive decline [10,11,12,13]

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