Lan Anat, Kalimian Michal, Amram Benjamin, Kofman Ora
Department of Psychology, Ben-Gurion University of the Negev, P.O.B. 653, Beer-Sheva, 84105, Israel.
Zlotowski Centre for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Environ Health. 2017 May 2;16(1):43. doi: 10.1186/s12940-017-0251-3.
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.
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（CPF）。孕妇接触CPF与出生体重降低、反射异常、智商下降以及母亲报告的广泛性发育障碍体征增加有关。本研究的目的是检查产前接触CPF对C57BL/6 J（B6）小鼠的长期影响，特别关注社交和重复行为。
在妊娠第12 - 15天，通过口服灌胃对B6雌性小鼠分别给予赋形剂、2.5 mg/kg CPF或5 mg/kg CPF。在出生后第6 - 12天（PND's），通过测量后代的3种新生儿反射来评估早期发育和神经运动能力。在成年期，即PND 90，使用社交偏好、社交新奇性和社交条件性位置偏好任务来研究社交行为。还在PND 90通过重复新颖物体接触任务（RNOC）评估物体识别和受限兴趣。为了排除CPF给药引起母性护理改变的可能性，通过母性找回任务评估母鼠的行为。
CPF处理导致PND's 6 - 12的新生儿反射发育延迟。在PND 90，产前接受5.0 mg/kg剂量CPF处理的小鼠在社交偏好测试中对陌生同种个体的偏好降低，社交条件性位置偏好也降低。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受限兴趣。CPF给药并未损害母鼠的行为，也未像在物体识别任务中观察到的那样导致记忆或识别缺陷。
我们的数据表明，孕期接触CPF对社交行为有长期有害影响，并限制对新颖物体的探索。
