Developmental nicotine exposure affects larval brain size and the adult dopaminergic system of Drosophila melanogaster.

BACKGROUND: Pregnant women may be exposed to nicotine if they smoke or use tobacco products, nicotine replacement therapy, or via e-cigarettes. Prenatal nicotine exposure has been shown to have deleterious effects on the nervous system in mammals including changes in brain size and in the dopaminergic system. The genetic and molecular mechanisms for these changes are not well understood. A Drosophila melanogaster model for these effects of nicotine exposure could contribute to faster identification of genes and molecular pathways underlying these effects. The purpose of this study was to determine if developmental nicotine exposure affects the nervous system of Drosophila melanogaster, focusing on changes to brain size and the dopaminergic system at two developmental stages. RESULTS: We reared flies on control or nicotine food from egg to 3rd instar larvae or from egg to adult and determined effectiveness of the nicotine treatment. We used immunohistochemistry to visualize the whole brain and dopaminergic neurons, using tyrosine hydroxylase as the marker. We measured brain area, tyrosine hydroxylase fluorescence, and counted the number of dopaminergic neurons in brain clusters. We detected an increase in larval brain hemisphere area, a decrease in tyrosine hydroxylase fluorescence in adult central brains, and a decrease in the number of neurons in the PPM3 adult dopaminergic cluster. We tested involvement of Dα7, one of the nicotinic acetylcholine receptor subunits, and found it was involved in eclosion, as previously described, but not involved in brain size. CONCLUSIONS: We conclude that developmental nicotine exposure in Drosophila melanogaster affects brain size and the dopaminergic system. Prenatal nicotine exposure in mammals has also been shown to have effects on brain size and in the dopaminergic system. This study further establishes Drosophila melanogaster as model organism to study the effects of developmental nicotine exposure. The genetic and molecular tools available for Drosophila research will allow elucidation of the mechanisms underlying the effects of nicotine exposure during development.

A Drosophila model for developmental nicotine exposure.

Despite the known health risks of tobacco smoking, many people including pregnant women continue smoking. The effects of developmental nicotine exposure are known, but the underlying mechanisms are not well understood. Drosophila melanogaster is a model organism that can be used for uncovering genetic and molecular mechanisms for drugs of abuse. Here I show that Drosophila can be a model to elucidate the mechanisms for nicotine's effects on a developing organism. Drosophila reared on nicotine food display developmental and behavioral effects similar to those in mammals including decreased survival and weight, increased developmental time, and decreased sensitivity to acute nicotine and ethanol. The Drosophila nicotinic acetylcholine receptor subunit alpha 7 (Dα7) mediates some of these effects. A novel role for Dα7 on ethanol sedation in Drosophila is also shown. Future research taking advantage of the genetic and molecular tools for Drosophila will allow additional discovery of the mechanisms behind the effects of nicotine during development.