Brain organoids reveal in detail the dangers of drinking alcohol during pregnancy

Drinking alcohol during pregnancy poses a serious threat
to the healthy development of the unborn baby.
There is no known safe amount
of alcohol to drink during pregnancy.

The consequences of prenatal alcohol exposure (PAE) are reflected in
different diagnoses of fetal alcohol spectrum disorder.
At one end of the spectrum, growth defects and physiological differences define fetal alcohol syndrome (FAS), but in most cases, irreversible brain damage leads to behavioral and learning challenges, even without physical impact
.
Experts estimate that 1.
1 — 5 percent of U.
S.
students — 1 in 20 — could be affected by PAE, some of whom experience FAS
.

While the clinical effects of fetal alcohol spectrum disorder 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 Psychiatry, researchers at the University of California San Diego School of Medicine used human brain organoids to more specifically document how alcohol exposure impairs the development and function
of new brain cells.

The findings highlight the widespread threat
of alcohol exposure to the fetal brain.
The harm caused is far-reaching and widespread," said
Dr.
Alysson R.
Muotri, professor in the Department of Pediatrics and Cellular and Molecular Medicine at the University of California, San Diego School of Medicine.

Using human-induced pluripotent stem cells, Muotri and his colleagues created three-dimensional brain organs that develop similarly to human fetal corticatogenesis—the formation of the outer layer of the brain, which contains many advanced functions such as reasoning, conscious thinking, emotional control, and language
.
Exposure to alcohol at different stages of fetal brain development can have different, but invariable, negative effects, ranging from fundamental dysfunction of cellular processes, to faulty construction of brain structures, insufficient production
of supporting cells (gliomagenesis) and connections between brain cells (synaptogenesis).
The researchers then monitored the electrical activity patterns of cortical organoids through electrophysiological recordings, recording and confirming damaged cortical organoid function
.

These findings improve on previous studies
conducted with animal models.
"They overcome suboptimal reproduction of non-human models," said co-author Miguel Del Campo, Ph.
D.
, an associate professor at the University of California, San Diego School of Medicine and a medical geneticist
at Reddy Children's Hospital in San Diego.
"In fact, they suggest that organoids are a valuable model for better, more comprehensive, and deeper assessment of the effects of
alcohol exposure on human brain development.
"

Co-author Kenneth L.
Jones, Ph.
D.
, professor of pediatrics at the University of California, San Diego School of Medicine, explains, "This is critical because we can better see which significant growth and signaling pathways are disrupted and may discover new targets that therapeutically block or prevent neuropathology
in prenatal alcohol exposure.
" The good news is that with specific experimental drugs, some of these alterations are reversed
.
”