Nicotine exposure in male mice may trigger ADHD in their offspring

Nicotine exposure has negative effects that echo down the generations – in mice, at least. Male mice exposed to nicotine had offspring with signs of a mouse version of attention deficit hyperactivity disorder (ADHD). Previous studies have emphasised that women risk the health of their children by smoking during pregnancy. It has been linked to their children’s risk of developing depression, asthma and polycystic ovary syndrome. There has been less focus on the effects of paternal cigarette use on the health of children, so Pradeep Bhide at Florida State University and his colleagues decided to investigate. They added nicotine to the water supply given to 12 male mice and, after 12 weeks, mated the males with females that had never been exposed to nicotine. None of the resulting offspring were ever directly exposed to nicotine. The team found these offspring were 30 to 50 per cent more active than expected. They also made at least 50 per cent more mistakes than mice usually do when trying to escape from a maze they had been familiarised with. Moreover, sons, but not daughters, of nicotine-exposed fathers spent less time exploring new objects — an indicator of attention deficiency.

Brain change

When Bhide and his colleagues looked into the mice’s brains, they found that those with nicotine-exposed fathers contained levels of dopamine that were 30 per cent lower than expected. They also had just half the dopamine receptors usually present in the mouse brain. Both characteristics are associated with ADHD, which may explain the hyperactivity and attention deficiency observed. No significant changes were found in the brains of female mice born to nicotine-exposed fathers. Bhide suspects that nicotine might have changed the gene expression in sperm via a process called transgenerational epigenetics. This would explain why the offspring, but not the fathers, showed ADHD-related behaviours – even though it was the fathers that were directly exposed to nicotine. His idea is supported by the nearly doubled level of DNA methylation — a key indicator of epigenetic changes — found in the sperm of nicotine-exposed mice. But why male offspring of nicotine-exposed mice suffer more from the effects than females remains a mystery. “Our data raise the possibility that some of the cognitive disabilities found in today’s children and adults may be attributed to adverse environmental factors suffered a generation ago,” says Bhide. But he points out that more research is required to understand whether the effects seen in mice are similar to those seen in humans.

New Scientist, 16 October 2018 ;