Valproic acid – a drug commonly used to treat epilepsy and bipolar disorder – can cause birth defects and developmental disorders if taken during pregnancy, but the reason why has long been a mystery.
This upset seems to occur around the time that the"neural tube" – a hollow tube of tissue that later becomes the brain and spinal cord – forms and closes. In human embryos, that's typically between the fourth and sixth week of pregnancy,To understand how valproic acid messes with this early stage of development, Keyes and his colleagues exposed mouse embryos to the drug.
How exactly does valproic acid push cells into senescence? It yanks the brakes off a specific gene that usually stays inactive throughout embryonic development, the team discovered.This gene codes for a molecule called p19Arf, which usually becomes active in adulthood and helps to clear cancerous and aging cells from the body. Although helpful in adults, the molecule's presence in embryos drives key cells into senescence and disrupts the development of the nervous system.
The organoid experiments confirmed which genes are affected by valproic acid exposure, and the mouse model revealed how the drug's effects unfold in ongoing pregnancies, he told Live Science in an email.For instance, the team exposed their mice and organoids to several high doses of valproic acid over a short period of time, whereas in real life, patients consistently take a lower dose of the drug over a longer time span.
"So then the child would ultimately be born with some defects in some population of cells," he said, and in theory,"this then gives rise to the cognitive and behavioral defects."
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