In research published in the August issue of Free Radical Biology and Medicine, U of T pharmacy and pharmacology professor Peter Wells and his colleagues determined that exposing pregnant mice only once to methamphetamine led to delivery of offspring with long-term neurodevelopmental problems, including reduced motor co-ordination. Methamphetamine is a potent and addictive stimulant.
"We've known for a while that meth abuse during pregnancy is associated with low birth weight, cleft palates and other malformations but this is the first research demonstrating that even a single exposure can cause long-term damage," says Wells. "It's pretty remarkable that a single low dose can have such an effect.
"It's an important finding, given the increasing use of club drugs among women of childbearing age. It has clinical implications, because it shows that the fetus is exquisitely sensitive."
The developing fetus appears to be vulnerable to DNA damage from methamphetamine exposure because it hasn't yet developed the enzymes that protect it against free radicals ?highly activated, destructive oxygen molecules that have been implicated in cancer and neurodegenerative diseases, says Wells. This vulnerability lasts from the embryonic stage through the later fetal period, times when organ structures and mental functions develop.
"People usually think the last trimester of pregnancy is when developing brain function is most susceptible to damage, but in this case the brain is also affected by methamphetamine even in the earlier embryonic period," says Wells.
Wells' next step will be to study women and their babies who have been exposed to drugs like methamphetamine that enhance free radical formation to see if the human damage is consistent with his mouse findi ngs. He will also try to determine whether the methamphetamine causes other lasting damage in mice, such as impacts on learning and memory.
"Methamphetamine has very different toxic effects in the fetal brain than in adult mice, which surprised me," says Wells. "In adults, you can see actual structural degeneration of the brain."
U of T doctoral candidates Winnie Jeng and Andrea Wong and undergraduate Ryan Ting-A-Kee were also involved in this study. The research was supported by a grant from the Canadian Institutes of Health Research (CIHR). The doctoral candidates received awards from the CIHR/Rx&D Health Research Foundation, the American Society of Toxicology and the Natural Sciences and Engineering Research Council of Canada.