Abstract
Alcohol exposure during gestation can lead to severe defects in brain development and lifelong physical, behavioral and learning deficits that are classified under the umbrella term fetal alcohol spectrum disorder (FASD). Sadly, FASD is diagnosed at an alarmingly high rate, affecting 2%–5% of live births in the United States, making it the most common non-heritable cause of mental disability. Currently, no standard therapies exist that are effective at battling FASD symptoms, highlighting a pressing need to better understand the underlying mechanisms by which alcohol affects the developing brain. While it is clear that sensory and cognitive deficits are driven by inappropriate development and remodeling of the neural circuits that mediate these processes, alcohol’s actions acutely and long-term on the brain milieu are diverse and complex. Microglia, the brain’s immune cells, have been thought to be a target for alcohol during development because of their exquisite ability to rapidly detect and respond to perturbations affecting the brain. Additionally, our view of these immune cells is rapidly changing, and recent studies have revealed a myriad of microglial physiological functions critical for normal brain development and long-term function. A clear and complete understanding of how microglial roles on this end of the spectrum may be altered in FASD is currently lacking. Such information could provide important insights toward novel therapeutic targets for FASD treatment. Here we review the literature that links microglia to neural circuit remodeling and provide a discussion of the current understanding of how developmental alcohol exposure affects microglial behavior in the context of developing brain circuits.
Highlights
The last decade has seen a renewed interest in microglial roles in the brain
The loss of functional plasticity, and concomitant microglial changes in the absence of P2Y12 signaling suggest that microglia actively participate in this form of plasticity and that purinergic signaling is critical to this process
No differences in either spine morphology or overall dendritic branching complexity were present. These findings suggest that developmental EtOH exposure can impair the formation of excitatory synapses, they do not address the dynamic nature of synapses, which are constantly remodeled as networks reorganize during plasticity
Summary
The last decade has seen a renewed interest in microglial roles in the brain. This has been spurred by new molecular and imaging technologies that have allowed scientists to explore the functions of these cells within intact neural tissue throughout the lifespan. Because microglia enter the brain early in development, they have the potential to influence the development of neural networks. We review the literature that has illuminated microglial contributions to the development of neural cells and their connectivity. We discuss how microglial behavior could contribute to alterations in neural network remodeling in the context of fetal alcohol spectrum. Spectrums: Microglial Functions and FASD disorder (FASD), a neurodevelopmental disorder caused by gestational exposure to ethanol that results in devastating sensory and cognitive deficits
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