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.

中文翻译：

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发育中的尼古丁暴露会影响幼虫的大脑大小和果蝇的多巴胺能成年系统。

背景技术孕妇吸烟或使用烟草产品，尼古丁替代疗法或通过电子烟可能会暴露于尼古丁。产前尼古丁暴露已显示对哺乳动物的神经系统具有有害作用，包括脑大小和多巴胺能系统的变化。这些变化的遗传和分子机制尚不十分清楚。果蝇黑斑病的果蝇模型可有助于更快地识别这些作用的基因和分子途径。这项研究的目的是确定发育性尼古丁暴露是否会影响果蝇的神经系统，重点是在两个发育阶段大脑大小和多巴胺能系统的变化。结果我们饲养了从卵到三龄幼虫或从卵到成年的对照或尼古丁食物，并确定了尼古丁治疗的有效性。我们使用免疫组化技术以酪氨酸羟化酶为标记物来观察整个大脑和多巴胺能神经元。我们测量了大脑面积，酪氨酸羟化酶荧光，并计算了大脑簇中多巴胺能神经元的数量。我们检测到幼虫大脑半球面积的增加，成人中枢大脑酪氨酸羟化酶荧光的减少，以及PPM3成人多巴胺能簇中神经元数量的减少。我们测试了烟碱乙酰胆碱受体亚基之一的Dα7的参与，发现它与前面提到的脱落有关，但不涉及大脑大小。结论我们得出结论，黑腹果蝇中发育性尼古丁暴露会影响大脑大小和多巴胺能系统。哺乳动物中的产前尼古丁暴露也已证明对大脑大小和多巴胺能系统有影响。这项研究进一步建立了果蝇果蝇作为模型生物，以研究发育性尼古丁暴露的影响。果蝇研究可利用的遗传和分子工具将阐明发育过程中尼古丁暴露影响的潜在机制。这项研究进一步建立了果蝇果蝇作为模型生物，以研究发育性尼古丁暴露的影响。果蝇研究可利用的遗传和分子工具将阐明发育过程中尼古丁暴露影响的潜在机制。这项研究进一步建立了果蝇果蝇作为模型生物，以研究发育性尼古丁暴露的影响。果蝇研究可利用的遗传和分子工具将阐明发育过程中尼古丁暴露影响的潜在机制。