A comparison of molecular alterations in environmental and genetic rat models of ADHD: a pilot study.
A comparison of molecular alterations in environmental and genetic rat models of ADHD: a pilot study.
复制标题
DOI：
10.1002/ajmg.b.30877
复制
发表时间：
2008-12-05
影响因子：
2.8
通讯作者：
Faraone, Stephen V.
中科院分区：
文献类型：
--
作者：
DasBanerjee, Tania;Middleton, Frank A.;Berger, David F.;Lombardo, John P.;Sagvolden, Terje;Faraone, Stephen V.
注意力缺陷多动障碍（ADHD）是学龄儿童最常见的神经行为障碍。除了遗传因素外，环境影响或基因×环境相互作用也在 ADHD 中发挥重要作用。经充分研究的 ADHD 环境风险因素之一是接触多氯联苯 (PCB)。在这项研究中，我们研究了基于自发性高血压大鼠 (SHR) 的完善的 ADHD 遗传模型和基于 PCB 的 ADHD 模型是否在涉及 ADHD 的脑回路中表现出相似的分子变化。在出生后 55-65 天收获 28 只雄性大鼠（8 只 SHR、8 只 Sprague-Dawley (SD) 对照、8 只 Wistar-Kyoto (WKY) 对照和 4 只暴露于 PCB 的 SD 大鼠）的大脑，并从 6 个感兴趣的大脑区域中分离出 RNA。使用 Rat RAE 230 2.0 GeneChip (Affymetrix) 对一组 308 个探针组的 RNA 表达差异进行分析，这些探针组询问 218 个被认为与 ADHD 或表观遗传基因调控高度相关的独特基因。通过实时定量 RT-PCR 证实了选定的观察结果。结果表明，SHR大鼠和PCB暴露的SD大鼠中Gnal、COMT、Adrbk1、Ntrk2、Hk1、Syt11和Csnk1a1基因的表达水平均发生改变。 Arrb2、Stx12、Aqp6、Syt1、Ddc 和 Pgk1 表达水平仅在 PCB 暴露的 SD 大鼠中发生变化。仅在 SHR 中表达发生改变的基因包括 Oprm1、Calcyon、Calmodulin、Lhx1 和 Hes6。表观遗传基因 Crebbp、Mecp2 和 Hdac5 在两种模型中均发生显着改变。这些数据提供了强有力的证据，表明基因和环境可以影响两种不同的 ADHD 模型中的不同基因组，但会导致类似的疾病样症状。
Attention Deficit Hyperactivity Disorder (ADHD) is the most common neurobehavioral disorder in school-aged children. In addition to genetic factors, environmental influences or gene × environmental interactions also play an important role in ADHD. One example of a well studied environmental risk factor for ADHD is exposure to polychlorinated biphenyls (PCBs). In this study, we investigated whether the well-established genetic model of ADHD based on the Spontaneously Hypertensive Rat (SHR) and a well established PCB-based model of ADHD exhibited similar molecular changes in brain circuits involved in ADHD. The brains from 28 male rats (8 SHR, 8 Sprague-Dawley (SD) controls, 8 Wistar-Kyoto (WKY) controls, and 4 PCB-exposed SD rats) were harvested at postnatal day 55-65 and RNA was isolated from six brain regions of interest. The RNA was analyzed for differences in expression of a set of 308 probe sets interrogating 218 unique genes considered highly relevant to ADHD or epigenetic gene regulation using the Rat RAE 230 2.0 GeneChip (Affymetrix). Selected observations were confirmed by real time quantitative RT-PCR. The results show that the expression levels of genes Gnal, COMT, Adrbk1, Ntrk2, Hk1, Syt11 and Csnk1a1 were altered in both the SHR rats and the PCB-exposed SD rats. Arrb2, Stx12, Aqp6, Syt1, Ddc and Pgk1 expression levels were changed only in the PCB-exposed SD rats. Genes with altered expression only in the SHRs included Oprm1, Calcyon, Calmodulin, Lhx1 and Hes6. The epigenetic genes Crebbp, Mecp2 and Hdac5 are significantly altered in both models. The data provide strong evidence that genes and environment can affect different set of genes in two different models of ADHD and yet result in the similar disease-like symptoms.
登录
查看更多内容
影响因子：
2.7
作者：
Berger, DF;Lombardo, JP;Quimby, F
通讯作者：
Quimby, F
DOI：
10.3109/15622970209150624
发表时间：
2002-10-01
期刊：
The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry
影响因子：
--
作者：
Bussing, Regina;Grudnik, Jennifer;Leonard, Christiana
通讯作者：
Leonard, Christiana
影响因子：
10.4
作者：
Bemis, JC;Seegal, RF
通讯作者：
Seegal, RF
影响因子：
3
作者：
Faraone, Stephen V;Biederman, Joseph
通讯作者：
Biederman, Joseph
影响因子：
10.4
作者：
Dziennis S;Yang D;Cheng J;Anderson KA;Alkayed NJ;Hurn PD;Lein PJ
通讯作者：
Lein PJ