De Felice Alessia, Scattoni Maria Luisa, Ricceri Laura, Calamandrei Gemma
Section of Neurotoxicology and Neuroendocrinology, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy; Department of Physiology and Pharmacology "Vittorio Erspamer", Sapienza University of Rome, Rome, Italy.
Section of Neurotoxicology and Neuroendocrinology, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
PLoS One. 2015 Mar 24;10(3):e0121663. doi: 10.1371/journal.pone.0121663. eCollection 2015.
Autism spectrum disorders are characterized by impaired social and communicative skills and repetitive behaviors. Emerging evidence supported the hypothesis that these neurodevelopmental disorders may result from a combination of genetic susceptibility and exposure to environmental toxins in early developmental phases. This study assessed the effects of prenatal exposure to chlorpyrifos (CPF), a widely diffused organophosphate insecticide endowed with developmental neurotoxicity at sub-toxic doses, in the BTBR T+tf/J mouse strain, a validated model of idiopathic autism that displays several behavioral traits relevant to the autism spectrum. To this aim, pregnant BTBR mice were administered from gestational day 14 to 17 with either vehicle or CPF at a dose of 6 mg/kg/bw by oral gavages. Offspring of both sexes underwent assessment of early developmental milestones, including somatic growth, motor behavior and ultrasound vocalization. To evaluate the potential long-term effects of CPF, two different social behavior patterns typically altered in the BTBR strain (free social interaction with a same-sex companion in females, or interaction with a sexually receptive female in males) were also examined in the two sexes at adulthood. Our findings indicate significant effects of CPF on somatic growth and neonatal motor patterns. CPF treated pups showed reduced weight gain, delayed motor maturation (i.e., persistency of immature patterns such as pivoting at the expenses of coordinated locomotion) and a trend to enhanced ultrasound vocalization. At adulthood, CPF associated alterations were found in males only: the altered pattern of investigation of a sexual partner, previously described in BTBR mice, was enhanced in CPF males, and associated to increased ultrasonic vocalization rate. These findings strengthen the need of future studies to evaluate the role of environmental chemicals in the etiology of neurodevelopment disorders.
自闭症谱系障碍的特征是社交和沟通技能受损以及重复行为。新出现的证据支持了这样一种假设，即这些神经发育障碍可能是由遗传易感性和发育早期接触环境毒素共同导致的。本研究评估了产前接触毒死蜱（CPF）的影响，毒死蜱是一种广泛扩散的有机磷杀虫剂，在亚毒性剂量下具有发育神经毒性，研究使用的是BTBR T+tf/J小鼠品系，这是一种经过验证的特发性自闭症模型，表现出与自闭症谱系相关的多种行为特征。为此，从妊娠第14天到17天，对怀孕的BTBR小鼠通过口服灌胃给予溶剂或剂量为6 mg/kg体重的CPF。两性后代都接受了早期发育里程碑的评估，包括身体生长、运动行为和超声发声。为了评估CPF的潜在长期影响，还在成年两性中检查了BTBR品系中通常会改变的两种不同社交行为模式（雌性与同性同伴的自由社交互动，或雄性与处于发情期雌性的互动）。我们的研究结果表明CPF对身体生长和新生儿运动模式有显著影响。接受CPF处理的幼崽体重增加减少，运动成熟延迟（即，以协调运动为代价的不成熟模式如旋转持续存在），并且有超声发声增强的趋势。在成年期，仅在雄性中发现了与CPF相关的改变：之前在BTBR小鼠中描述的对性伴侣的调查模式改变在接受CPF处理的雄性中增强，并且与超声发声率增加相关。这些发现强化了未来研究评估环境化学物质在神经发育障碍病因学中作用的必要性。
