Developmental and behavioral alterations in zebrafish embryonically exposed to valproic acid (VPA): An aquatic model for autism.
Developmental and behavioral alterations in zebrafish embryonically exposed to valproic acid (VPA): An aquatic model for autism.
复制标题
DOI：
10.1016/j.ntt.2018.01.002
复制
发表时间：
2018-03
影响因子：
2.9
通讯作者：
Huang C
中科院分区：
文献类型：
--
作者：
Chen J;Lei L;Tian L;Hou F;Roper C;Ge X;Zhao Y;Chen Y;Dong Q;Tanguay RL;Huang C
自闭症谱系障碍（ASD）具有复杂的神经发育障碍及其起源，与遗传和环境因素有关。因此，迫切需要建立具有ASD样特征的动物模型，以了解ASD的潜在机制。产前暴露于丙戊酸（VPA）已被证明在人类、大鼠和最近的斑马鱼中引起asd样症状。本研究利用VPA暴露建立斑马鱼ASD模型，并通过观察斑马鱼胚胎和幼鱼大脑发育中的ASD样表型和行为改变来验证该模型。我们的研究结果表明，在受精后8小时（hpf）开始用VPA处理斑马鱼胚胎可显著增加ASD大头畸形表型；胚胎/幼虫运动行为过度活跃；类自闭症幼虫社会行为增加。进一步分析显示，VPA暴露后，细胞增殖增加，成熟新生神经元比例增加，大脑区域神经干细胞增殖增加，这可能导致大脑过度生长和大头畸形。我们的研究表明，VPA暴露可以产生ASD样表型和行为，表明斑马鱼作为ASD及其潜在机制研究的替代模型的有效性。
Autism spectrum disorder (ASD) has complex neurodevelopmental impairments and origins that are linked to both genetic and environmental factors. Hence, there is an urgency to establish animal models with ASD-like characteristics to understand the underlying mechanisms of ASD. Prenatal exposure to valproic acid (VPA) has been shown to cause ASD-like symptoms in humans, rats, and recently zebrafish. The present study investigated the use of VPA exposure to create an ASD model in zebrafish that was verified through observation of ASD-like phenotypes in brain development and behavioral changes in embryonic and larval zebrafish. Our findings revealed that treating zebrafish embryos with VPA starting at 8 hours post fertilization (hpf) resulted in significant: increase in the ASD macrocephalic phenotype; hyperactivity of embryo/larvae movement behaviors; and increases of ASD-like larval social behaviors. Further analysis showed increases in cell proliferation, the proportion of mature newborn neurons, and neural stem cell proliferation in the brain region, which may contribute to the brain overgrowth and macrocephaly observed following VPA exposure. Our study demonstrated that VPA exposure can generate ASD-like phenotypes and behaviors, showing the validity of zebrafish as an alternative model for ASD and underlying mechanism research.
登录
查看更多内容
影响因子：
2.9
作者：
Buske, Christine;Gerlai, Robert
通讯作者：
Gerlai, Robert
影响因子：
3.4
作者：
MacPhail, R. C.;Brooks, J.;Padilla, S.
通讯作者：
Padilla, S.
慢性 PFOS 暴露会导致成年斑马鱼出现生命阶段特定的行为缺陷，并导致 F1 后代出现畸形和行为缺陷
影响因子：
4.1
作者：
Chen, Jiangfei;Das, Siba R.;La Du, Jane;Corvi, Margaret M.;Bai, Chenglian;Chen, Yuanhong;Liu, Xiaojuan;Zhu, Guonian;Tanguay, Robert L.;Dong, Qiaoxiang;Huang, Changjiang
通讯作者：
Huang, Changjiang
非单调剂量反应关系和内分泌破坏者：一种定性评估方法。
DOI：
10.1186/1476-069x-14-13
发表时间：
2015-02-11
期刊：
Environmental health : a global access science source
影响因子：
--
作者：
Lagarde F;Beausoleil C;Belcher SM;Belzunces LP;Emond C;Guerbet M;Rousselle C
通讯作者：
Rousselle C
影响因子：
2.9
作者：
Chen J;Huang C;Zheng L;Simonich M;Bai C;Tanguay R;Dong Q
通讯作者：
Dong Q