Translational outcomes relevant to neurodevelopmental disorders following early life exposure of rats to chlorpyrifos.
Translational outcomes relevant to neurodevelopmental disorders following early life exposure of rats to chlorpyrifos.
复制标题
与神经发育障碍有关的转化结果与大鼠早期生命暴露后有关。
DOI：
10.1186/s11689-020-09342-1
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发表时间：
2020-12-16
影响因子：
4.9
通讯作者：
Silverman JL
中科院分区：
文献类型：
--
作者：
Berg EL;Ching TM;Bruun DA;Rivera JK;Careaga M;Ellegood J;Lerch JP;Wöhr M;Lein PJ;Silverman JL
神经发育障碍（ndd），包括智力残疾、注意缺陷多动障碍（ADHD）和自闭症谱系障碍（ASD），是普遍存在的终身疾病，药物干预措施并不容易获得。ndd患病率在相对较短时间内的大幅增加可能不能仅仅归因于遗传因素和/或改进的诊断标准。目前已有共识认为，神经发育关键时期的多基因位点与环境风险因素共同影响NDD的易感性和症状严重程度。有机磷农药已被确定为潜在的环境危险因素。流行病学研究表明，产前暴露于农药毒死蜱（CPF）的儿童有显著的智力和运动迟缓，并且与智力迟缓或残疾、ADHD或ASD的临床诊断有很强的正相关。我们检验了发育性CPF暴露会损害与NDD表型相关的行为（即社会沟通缺陷和重复、限制性行为）的假设。从出生后1-4天开始，雄性和雌性大鼠仔暴露于0.1、0.3或1.0 mg/kg （s.c）的CPF。这些CPF剂量没有显著抑制血液或大脑中的乙酰胆碱酯酶活性，但显著损害了雌雄幼犬的超声波发声（USV）。在暴露于0.3 mg/kg和1.0 mg/kg CPF的雌性幼鱼中，通过50-kHz USV播放的积极亲和性社会交往缺失。相比之下，CPF暴露模式对大运动能力或情境和线索恐惧记忆没有显著影响。体外磁共振成像在cpf暴露大鼠和相应的对照物之间使用严格的错误发现校正基本没有差异；然而，在0.3 mg/kg剂量组中，女性有有趣的趋势。这项工作产生并表征了一个大鼠发育CPF暴露模型，该模型显示出围产期暴露水平对大脑或血液中乙酰胆碱酯酶活性没有显著抑制而导致的不良行为表型。这些数据表明，目前有关CPF安全水平的规定需要重新考虑。在线版本包含补充材料，可在10.1186/s11689-020-09342-1获得。
Neurodevelopmental disorders (NDDs), including intellectual disability, attention deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD), are pervasive, lifelong disorders for which pharmacological interventions are not readily available. Substantial increases in the prevalence of NDDs over a relatively short period may not be attributed solely to genetic factors and/or improved diagnostic criteria. There is now a consensus that multiple genetic loci combined with environmental risk factors during critical periods of neurodevelopment influence NDD susceptibility and symptom severity. Organophosphorus (OP) pesticides have been identified as potential environmental risk factors. Epidemiological studies suggest that children exposed prenatally to the OP pesticide chlorpyrifos (CPF) have significant mental and motor delays and strong positive associations for the development of a clinical diagnosis of intellectual delay or disability, ADHD, or ASD. We tested the hypothesis that developmental CPF exposure impairs behavior relevant to NDD phenotypes (i.e., deficits in social communication and repetitive, restricted behavior). Male and female rat pups were exposed to CPF at 0.1, 0.3, or 1.0 mg/kg (s.c.) from postnatal days 1-4. These CPF doses did not significantly inhibit acetylcholinesterase activity in the blood or brain but significantly impaired pup ultrasonic vocalizations (USV) in both sexes. Social communication in juveniles via positive affiliative 50-kHz USV playback was absent in females exposed to CPF at 0.3 mg/kg and 1.0 mg/kg. In contrast, this CPF exposure paradigm had no significant effect on gross locomotor abilities or contextual and cued fear memory. Ex vivo magnetic resonance imaging largely found no differences between the CPF-exposed rats and the corresponding vehicle controls using strict false discovery correction; however, there were interesting trends in females in the 0.3 mg/kg dose group. This work generated and characterized a rat model of developmental CPF exposure that exhibits adverse behavioral phenotypes resulting from perinatal exposures at levels that did not significantly inhibit acetylcholinesterase activity in the brain or blood. These data suggest that current regulations regarding safe levels of CPF need to be reconsidered. The online version contains supplementary material available at 10.1186/s11689-020-09342-1.
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影响因子：
5.8
作者：
ELLMAN, GL;COURTNEY, KD;FEATHERSTONE, RM
通讯作者：
FEATHERSTONE, RM
聚类自闭症：在26个小鼠模型中使用神经解剖学差异来深入了解异质性。
影响因子：
11
作者：
Ellegood, J.;Anagnostou, E.;Babineau, B. A.;Crawley, J. N.;Lin, L.;Genestine, M.;DiCicco-Bloom, E.;Lai, J. K. Y.;Foster, J. A.;Penagarikano, O.;Geschwind, D. H.;Pacey, L. K.;Hampson, D. R.;Laliberte, C. L.;Mills, A. A.;Tam, E.;Osborne, L. R.;Kouser, M.;Espinosa-Becerra, F.;Xuan, Z.;Powell, C. M.;Raznahan, A.;Robins, D. M.;Nakai, N.;Nakatani, J.;Takumi, T.;van Eede, M. C.;Kerr, T. M.;Muller, C.;Blakely, R. D.;Veenstra-VanderWeele, J.;Henkelman, R. M.;Lerch, J. P.
通讯作者：
Lerch, J. P.
影响因子：
4.7
作者：
Burke RD;Todd SW;Lumsden E;Mullins RJ;Mamczarz J;Fawcett WP;Gullapalli RP;Randall WR;Pereira EFR;Albuquerque EX
通讯作者：
Albuquerque EX
DOI：
10.1002/aur.1925
发表时间：
2018-04
期刊：
Autism research : official journal of the International Society for Autism Research
影响因子：
--
作者：
Berg EL;Copping NA;Rivera JK;Pride MC;Careaga M;Bauman MD;Berman RF;Lein PJ;Harony-Nicolas H;Buxbaum JD;Ellegood J;Lerch JP;Wöhr M;Silverman JL
通讯作者：
Silverman JL
影响因子：
5.7
作者：
Genovese, CR;Lazar, NA;Nichols, T
通讯作者：
Nichols, T