A closer look at the effects of alcohol on developing brains using organoids

A closer look at the effects of alcohol on developing brains using organoids

Drinking alcohol while pregnant significantly jeopardizes the unborn child’s ability to develop normally. There is no alcohol intake that is known to be safe during pregnancy.

The various diseases that fall under the general category of fetal alcohol spectrum disorders reflect the effects of prenatal alcohol exposure (PAE). Fetal alcohol syndrome (FAS) is characterized at one end of the spectrum by development delays and physical abnormalities, but in the majority of cases, irreparable brain damage causes behavior and learning difficulties even in the absence of physical effects. According to experts, between 1 and 5 percent of kids in the United States, or as many as 1 in 20, may have PAE, with some also having FAS.

The specific molecular effects of fetal alcohol spectrum diseases on the human fetal cerebral cortex are not entirely known, despite the fact that the clinical impacts of these illnesses are extensively characterized. In a recent study, researchers from the University of California San Diego School of Medicine used human brain organoids to more precisely demonstrate how alcohol exposure impairs the development and functionality of new brain cells. The findings were published on November 16, 2022 in the journal Molecular Psychiatry.

According to Alysson R. Muotri, PhD, professor in the departments of pediatrics and cellular and molecular medicine at the UC San Diego School of Medicine, the results highlight the significant risk that alcohol exposure poses to the developing brain and the harm perpetrated is substantial and widespread.

Cleber A. Trujillo, a former project scientist in Muotri’s lab who is currently associate director of stem cell biology at Massachusetts-based Vesalius Therapeutics, and Muotri are co-corresponding authors on the paper.

Muotri and colleagues developed three-dimensional brain organoids from human induced pluripotent stem cells that develop in a manner similar to human fetal corticogenesis, or the development of the outer layers of the brain that contain many high-level functions like reasoning, conscious thought, emotional control, and speech.

Alcohol exposure had a variety of detrimental impacts on the developing fetal brain, all of which were always harmful. These effects ranged from fundamental cellular malfunction to poor brain architecture to insufficient gliogenesis and connections between brain cells (synaptogenesis).

The scientists then used electrophysiological recordings to track the electrical activity patterns in the cortical organoids to validate and verify the reduced function of the cortical organoids.

According to the authors, the results outperform those of earlier research that used animal models.

According to co-author Miguel Del Campo, MD, PhD, an assistant professor at the UC San Diego School of Medicine and a medical geneticist at Rady Children’s Hospital-San Diego, they overcome the unsatisfactory recapitulation of non-human animals. They demonstrate that organoids are a useful model for more accurately and thoroughly evaluating the effects of alcohol exposure on the developing human brain.

According to co-author Kenneth L. Jones, MD, professor of pediatrics at UC San Diego School of Medicine, the research is crucial because we can better see what prominent growth and signaling pathways are disrupted and possibly discover new targets to therapeutically inhibit or prevent the neuropathology of prenatal alcohol exposure. The good news is that several experimental medications were able to undo some of these modifications.

Sources:

Adams, J.W., Negraes, P.D., Truong, J. et al. (2022). Impact of alcohol exposure on neural development and network formation in human cortical organoids. Mol Psychiatry. https://doi.org/10.1038/s41380-022-01862-7

https://today.ucsd.edu/story/brain-organoids-reveal-in-detail-the-harms-of-prenatal-alcohol-exposure