HomeHealthMedicineBrain organoids reveal in detail the harms of

Brain organoids reveal in detail the harms of

image: Lab-grown brain organoids are helping researchers explore the early stages of human brain development.
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Credit: UC San Diego Health Sciences

Alcohol consumption during pregnancy poses a significant risk to the healthy development of the unborn child. There is no known safe amount of alcohol during pregnancy.

The consequences of prenatal alcohol exposure (PAE) are reflected in the various diagnoses that arise under the umbrella of fetal alcohol spectrum disorders. At one end of the spectrum, stunted growth and physical differences define fetal alcohol syndrome (FAS), but in most cases, irreversible brain damage leads to behavioral and learning problems even without a physical impact. Experts estimate that 1.1 to 5 percent of American schoolchildren — as many as 1 in 20 — may be affected by PAE, with a percentage experiencing FAS.

Although the clinical effects of fetal alcohol spectrum disorders are well documented, the precise molecular effects on the human fetal cerebral cortex are not fully understood. In a new study, published Nov. 16, 2022 in Molecular Psychiatryresearchers at the University of California San Diego School of Medicine used organoids from the human brain to more specifically document how exposure to alcohol impairs the development and functioning of new brain cells.

“The findings underscore the broad threat of alcohol exposure to the fetal brain. The damage done is profound and extensive,” said Alysson R. Muotri, PhD, professor in the Departments of Pediatrics and Cellular and Molecular Medicine at the UC San Diego School of Medicine.

Muotri is co-corresponding author of the study with Cleber A. Trujillo, a former project scientist in Muotri’s lab and now associate director of stem cell biology at Vesalius Therapeutics in Massachusetts.

Using human-induced pluripotent stem cells, Muotri and colleagues created three-dimensional brain organoids that develop similarly to human fetal corticogenesis — the formation of the brain’s outer layers that house many high-level functions, such as reasoning, conscious thinking, emotional control. . and speech.

Exposure to alcohol at different points in the development of the fetal brain resulted in various but always negative effects, from fundamental dysfunction of cellular processes to a defective brain architecture and insufficient formation of support cells (gliogenesis) and connections between brain cells (synaptogenesis).

The researchers followed by performing electrophysiological recordings to monitor electrical activity patterns in the cortical organoids, documenting and confirming impaired cortical organoid function.

The authors said the findings are better than previous animal model studies.

“They overcome the suboptimal recapitulation of non-human models,” said study co-author Miguel Del Campo, MD, PhD, associate professor at the UC San Diego School of Medicine and medical geneticist at Rady Children’s Hospital-San Diego. “They even show that organoids are a valuable model to better, more fully and in depth assess the effects of alcohol exposure on the developing human brain.”

Co-author Kenneth L. Jones, MD, a professor of pediatrics at the UC San Diego School of Medicine, explained, “That’s crucial because we can better see which prominent growth and signaling pathways are disrupted and perhaps discover new targets to therapeutically target.” hinder or prevent the neuropathology of prenatal alcohol exposure. The good news is that some of these changes were reversed using specific experimental drugs.”

Co-authors include: Jason W. Adams, Priscilla D. Negraes, Justin Truong, Timothy Tran, Ryan Szeto, Carmen Teodorof, and Stephen A. Spector, all of UC San Diego.

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