Dysregulation of autism-associated synaptic proteins by psychoactive pharmaceuticals at environmental concentrations.
Dysregulation of autism-associated synaptic proteins by psychoactive pharmaceuticals at environmental concentrations.
复制标题
DOI：
10.1016/j.neulet.2017.09.058
复制
发表时间：
2017-11-20
影响因子：
2.5
通讯作者：
Thomas MA
中科院分区：
文献类型：
--
作者：
Kaushik G;Xia Y;Pfau JC;Thomas MA
自闭症谱系障碍（ASD）是一种复杂的神经系统疾病，目前在美国的患病率估计为每50个儿童中有1个。大多数儿童特发性自闭症病例可能是由遗传易感个体中未知的环境触发因素引起的。这些触发因素可能包括母体通过净化效果不佳的饮用水使发育中的胚胎接触到与环境相关的微量精神活性药物。我们实验室之前的研究考察了在环境浓度的精神活性药物治疗下，与神经元发育相关的基因组在胖头鲦鱼大脑中的上调和下调（富集）程度。本研究的目的是确定类似的治疗是否会改变asd相关突触蛋白在分化的人类神经细胞上的体外表达。将人SK-N-SH神经母细胞瘤细胞在10μM维甲酸（RA）下分化2周，再用环境相关浓度的氟西汀、卡马西平或文拉法辛处理，流式细胞术分析asd相关突触蛋白的表达。数据显示，卡马西平单独、文拉法辛单独以及环境浓度下的混合处理显著改变了关键突触蛋白（NMDAR1、PSD95、SV2A、HTR1B、HTR2C和OXTR）的表达。数据表明，极低浓度的精神活性药物改变了关键突触蛋白的体外表达，这些蛋白可能通过破坏神经元发育而导致ASD等神经系统疾病。
Autism Spectrum Disorders (ASD) are complex neurological disorders for which the prevalence in the U.S. is currently estimated to be 1 in 50 children. A majority of cases of idiopathic autism in children likely result from unknown environmental triggers in genetically susceptible individuals. These triggers may include maternal exposure of a developing embryo to environmentally relevant minute concentrations of psychoactive pharmaceuticals through ineffectively purified drinking water. Previous studies in our lab examined the extent to which gene sets associated with neuronal development were up- and down-regulated (enriched) in the brains of fathead minnows treated with psychoactive pharmaceuticals at environmental concentrations. The aim of this study was to determine whether similar treatments would alter in vitro expression of ASD-associated synaptic proteins on differentiated human neuronal cells. Human SK-N-SH neuroblastoma cells were differentiated for two weeks with 10μM retinoic acid (RA) and treated with environmentally relevant concentrations of fluoxetine, carbamazepine or venlafaxine, and flow cytometry technique was used to analyze expression of ASD-associated synaptic proteins. Data showed that carbamazepine individually, venlafaxine individually and mixture treatment at environmental concentrations significantly altered the expression of key synaptic proteins (NMDAR1, PSD95, SV2A, HTR1B, HTR2C and OXTR). Data indicated that psychoactive pharmaceuticals at extremely low concentrations altered the in vitro expression of key synaptic proteins that may potentially contribute to neurological disorders like ASD by disrupting neuronal development.
登录
查看更多内容
在环境浓度下，孕产妇接触卡马西平可以横穿肠道和胎盘屏障。
DOI：
10.1016/j.bbrc.2016.04.088
发表时间：
2016-05-27
影响因子：
3.1
作者：
Kaushik G;Huber DP;Aho K;Finney B;Bearden S;Zarbalis KS;Thomas MA
通讯作者：
Thomas MA
影响因子：
3
作者：
Kaushik G;Thomas MA;Aho KA
通讯作者：
Aho KA
影响因子：
3
作者：
Cope, Georgina;Kaushik, Gaurav;Healy, Vincent
通讯作者：
Healy, Vincent
DOI：
10.1080/15287394.2013.865107
发表时间：
2014-03-19
影响因子：
2.6
作者：
Melvin, Steven D.;Cameron, Mark C.;Lanctot, Chantal M.
通讯作者：
Lanctot, Chantal M.
影响因子：
6.4
作者：
Nelson, Peter T.;Wang, Wang-Xia;Rajeev, Bernard W.
通讯作者：
Rajeev, Bernard W.