Nicotine use in male mice can affect brain function in their grandchildren

Current estimates suggest that there are nearly 38 million people in the US who smoke cigarettes and an estimated 10.8 million people use e-cigarettes with this number rising every year. Nicotine is an addictive drug found in both conventional cigarettes as well as e-cigarettes, cigars, and hookah. Many of the harmful effects of smoking in adults are not attributed to nicotine however, there exist significant risks in pregnant women relating to the developing fetus including: abnormal brain development, type-2 diabetes, obesity, hypertension, and respiratory dysfunction. There has also been a number of studies linking paternal smoking habits with attention deficit and hyperactive disorder (ADHD) and problems with attention control in offspring. Unfortunately, human studies often have difficulties separating maternal or paternal smoking effects from other environmental or genetic effects. To answer this question in a more controlled manner, a team of researchers from Florida turned to a mouse model of brain development.

The team of researchers exposed male mice to nicotine in their water for 12 weeks and then bred them to female mice who had never seen nicotine before. The researchers saw evidence of hyperactivity, attention deficit, and cognitive difficulties in both the male and female children. When the team bred this generation of mice with ones who had never been exposed to nicotine they saw that these offspring (the grandchildren to the original mice) also had problems with learning and cognitive development even though their parents had never directly consumed nicotine. Additionally, the team was able to show that the changes in brain development could be traced back to changes in the epigenetics of the original males sperm.

Epigenetics is a way for our cells to fine tune the expression of certain genes in our cells. Its how we turn cells into skin cells, brain cells, or heart cells even though they all have the same DNA. Epigenetics is like a light switch; it is able to turn on or turn off certain genes depending on what each cell needs in order to do its function. Here is a good video to understand how epigenetics works. In this study, the team found that there was a significant change in the epigenetic marks, here called methylation marks, on a gene for the dopamine receptor. The researchers theorize that these methylation marks are passed from father to children to grandchildren and that they are responsible for the defects in brain development seen.

This research highlights an important point; the paternal health is also important in helping determine the health of the offspring. Many of our current chronic diseases could trace their origins to some exposure our grandparents received which influenced our parent’s epigenetics and our epigenetics. There are a few things to consider about this paper: 1) this was done in mice and so it will be important to show that the same methylation marks exist in people, 2) we need to find evidence that these marks are passed from one generation to the next in order to implicate them in the trans-generational effects of nicotine, 3) most people do not drink nicotine so work showing how this may differ if the drug was inhaled would be important to consider. It is clear that nicotine in any form should be avoided by both mother and father if they are trying to conceive a child. More work needs to be done to understand what other diseases may be passed through the generations.

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