Prenatal chlorpyrifos leads to autism-like deficits in C57Bl6/J mice.
Prenatal chlorpyrifos leads to autism-like deficits in C57Bl6/J mice.
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DOI：
10.1186/s12940-017-0251-3
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发表时间：
2017-05-02
期刊：
影响因子：
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通讯作者：
Kofman O
中科院分区：
文献类型：
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作者：
Lan A;Kalimian M;Amram B;Kofman O
儿童每天都有接触有机磷杀虫剂的风险，其中最常见的是毒死蜱。孕妇暴露于CPF与出生体重下降，反射异常，智商降低以及普遍性发育障碍体征的母亲报告增加有关。本研究的目的是研究产前暴露于CPF对C57 BL/6 J（B6）小鼠的长期影响，特别是对社会和重复行为的影响。B6雌性小鼠在妊娠第12-15天通过经口管饲法用媒介物、2.5mg/kg CPF或5 mg/kg CPF处理。在出生后第6-12天，通过测量后代的3个新生儿反射来评估早期发育和神经运动能力。在成年后，PND 90，社会行为进行了调查，社会偏好，社会新奇性和社会条件性位置偏好任务。对象识别和限制的兴趣，测量重复的新物体接触任务（RNOC），也进行了评估PN D 90。为了排除CPF给药引起母体护理改变的可能性，通过母体检索任务评价母鼠的行为。CPF治疗导致PND 6-12时新生儿反射发育延迟。PND 90时，产前接受5.0 mg/kg剂量给药的小鼠在社会偏好测试中表现出对不熟悉同种动物的偏好降低，并表现出社会条件性位置偏好降低。在RNOC任务中，产前暴露于2.5 mg/kg剂量CPF的小鼠表现出增强的限制性兴趣。CPF给药不会损害母鼠的行为，也不会引起记忆或识别缺陷，如在物体识别任务中所观察到的。我们的数据表明，妊娠期暴露于CPF对社会行为有长期的有害影响，并限制了对新对象的探索。
Children are at daily risk for exposure to organophosphate insecticides, of which the most common is chlorpyrifos (CPF). Exposure of pregnant women to CPF was linked to decreased birth weight, abnormal reflexes, reduction in IQ, as well as increased maternal reports of signs of pervasive developmental disorder. The aim of current study was to examine the long term effects of prenatal exposure to CPF in C57BL/6 J (B6) mice with specific focus on social and repetitive behavior. B6 female mice were treated with vehicle, 2.5 mg/kg CPF or 5 mg/kg of CPF on gestational days 12–15 by oral gavage. On postnatal days (PND’s) 6–12 early development and neuromotor ability were assessed by measuring 3 neonatal reflexes in the offspring. In adulthood, PND 90, social behavior was investigated using the social preference, social novelty and social conditioned place preference tasks. Object recognition and restricted interest, measured by the repetitive novel object contact task (RNOC), were also assessed on PN D 90. In order to rule out the possibility that CPF administration induced alterations in maternal care, the dams’ behavior was evaluated via the maternal retrieval task. CPF treatment resulted in delayed development of neonatal reflexes on PND’s 6–12. On PND 90, mice treated prenatally with the 5.0 mg/kg dose exhibited reduced preference towards an unfamiliar conspecific in the social preference test and reduced social conditioned place preference. In the RNOC task, mice exposed prenatally to 2.5 mg/kg dose of CPF showed enhanced restricted interest. CPF administration did not impair dams’ behavior and did not cause memory or recognition deficit as was observed in the object recognition task. Our data indicate that gestational exposure to CPF has long-term deleterious effects on social behavior and limits exploration of novel objects.