Researchers from the Medical College of Georgia (MCG) conducted a study and found that CDP-choline, a dietary supplement sold as a brain-boosting agent and being tested as a treatment for stroke and traumatic brain injury, may block brain damage that can result from alcohol consumption early in pregnancy. Dr. Erhard Bieberich, biochemist in the MCG Schools of Graduate Studies and Medicine led the study, and Dr. Guanghu Wang, a research scientist at MCG, was the study’s co-author.
The article, published in Cell Death and Disease, explains that alcohol consumption in early pregnancy increases levels of a lipid called ceramide, which significantly increases cell death among cells critical to skull and brain formation. Resulting neural crest damage includes the brain’s "skin" (the multi-layered meninges that provides protection and nourishment) producing less TGF-β1, a growth factor that is critical for brain and bone development. This finding may help explain the cranial bone and cognitive defects that can result in fetal alcohol syndrome.
Dr. Bieberich explained that “there is just a little window,” about four weeks after conception, when neural crest cells emerge for a few days before morphing into other cell types that help form numerous organs. This is often before a woman knows she is pregnant. The studies indicate the potential for lasting damage to the fetus if a woman drinks, for example, several glasses of wine within an hour during that window.
Because ceramide is known to induce cell death and be activated by alcohol, the researchers thought it could be a culprit for the damage caused during pregnancy. They found high levels of ceramide both in mouse cells and pregnant mice exposed to alcohol along with a five-fold increase in apoptotic (or dying) cells. "There is a clear correlation," Dr. Bieberich said.
They also found that neural crust cells aren’t as touch and replaceable as they once thought; in fact, 25 percent of mouse embryos exposed to alcohol during that critical period had defects in the fibrous joints that connect the skull. "You get a snowball effect: The neural crest is damaged, the meninges doesn’t develop properly, and tissue-like bone and brain that are regulated by the meninges don’t develop properly either," Dr. Bieberich said.
When the researchers added ceramide-neutralizing CDP-choline to the mouse cells, cell death and ceramide levels were reduced. Alcohol prompts the body to produce more ceramide from the brain lipid sphingomyelin, a major component of cell membranes. The researchers found that CDP-choline pushes back toward producing less ceramide, preventing damage as long as the drinking stops.
"Ceramide can be bad or good," notes Dr. Bieberich, who has shown, for example, ceramide’s role in helping early stem cells evolve into embryonic tissue. But alcohol upsets the natural balance.
Follow-up studies, funded by the March of Dimes, include determining whether CDP-choline can rescue cells after the fact or whether it or a similar supplement would need to be taken preventively.
"Hopefully we can rescue some of the cells by triggering or signaling the back reaction," Dr. Bieberich said. He also wants to see if CDP-choline affords the same protection in pregnant mice that it does in laboratory cells.
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