Department of Biology, University at Albany, SUNY, Albany, NY 12222, USA.
Neurotoxicology. 2009 Mar;30(2):305-11. doi: 10.1016/j.neuro.2009.01.004. Epub 2009 Jan 21.
We developed Drosophila melanogaster as a model to study correlated behavioral, neuronal and genetic effects of the neurotoxin lead, known to affect cognitive and behavioral development in children. We showed that, as in vertebrates, lead affects both synaptic development and complex behaviors (courtship, fecundity, locomotor activity) in Drosophila. By assessing differential behavioral responses to developmental lead exposure among recombinant inbred Drosophila lines (RI), derived from parental lines Oregon R and Russian 2b, we have now identified a genotype by environment interaction (GEI) for a behavioral trait affected by lead. Drosophila Activity Monitors (TriKinetics, Waltham, MA), which measure activity by counting the number of times a single fly in a small glass tube walks through an infrared beam aimed at the middle of the tube, were used to measure activity of flies, reared from eggs to 4 days of adult age on either control or lead-contaminated medium, from each of 75 RI lines. We observed a significant statistical association between the effect of lead on Average Daytime Activity (ADA) across lines and one marker locus, 30AB, on chromosome 2; we define this as a Quantitative Trait Locus (QTL) associated with behavioral effects of developmental lead exposure. When 30AB was from Russian 2b, lead significantly increased locomotor activity, whereas, when 30AB was from Oregon R, lead decreased it. 30AB contains about 125 genes among which are likely "candidate genes" for the observed lead-dependent behavioral changes. Drosophila are thus a useful, underutilized model for studying behavioral, synaptic and genetic changes following chronic exposure to lead or other neurotoxins during development.
我们开发了黑腹果蝇作为模型,研究神经毒素铅的相关行为、神经元和遗传效应,已知铅会影响儿童的认知和行为发育。我们表明,与脊椎动物一样,铅会影响突触发育和果蝇的复杂行为(求偶、繁殖力、运动活性)。通过评估来自亲本品系俄勒冈 R 和俄罗斯 2b 的重组近交系(RI)果蝇对发育性铅暴露的差异行为反应,我们现在已经确定了一个受铅影响的行为特征的基因型与环境互作(GEI)。果蝇活动监测器(TriKinetics,马萨诸塞州沃尔瑟姆)通过计算一只在小玻璃管中行走的单只果蝇穿过指向管中间的红外光束的次数来测量活动,用于测量从卵中饲养到成年后 4 天的 flies 的活动,无论是在对照或受铅污染的培养基中,来自 75 个 RI 品系中的每一个。我们观察到铅对跨线平均日间活动(ADA)的影响与染色体 2 上的一个标记基因座 30AB 之间存在显著的统计学关联;我们将其定义为与发育性铅暴露的行为效应相关的数量性状基因座(QTL)。当 30AB 来自俄罗斯 2b 时,铅显著增加了运动活性,而当 30AB 来自俄勒冈 R 时,铅则降低了它。30AB 包含大约 125 个基因,其中可能有“候选基因”参与了观察到的依赖于铅的行为变化。因此,果蝇是一种有用的、未充分利用的模型,可用于研究在发育过程中慢性暴露于铅或其他神经毒素后行为、突触和遗传变化。