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A comparison of molecular alterations in environmental and genetic rat models of ADHD: a pilot study.

ABSTRACT: Attention deficit hyperactivity disorder (ADHD) is the most common neurobehavioral disorder in school-aged children. In addition to genetic factors, environmental influences or gene x 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 days (PNDs) 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 RAE230 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.

SUBMITTER: DasBanerjee T

PROVIDER: S-EPMC2587509 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature

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A comparison of molecular alterations in environmental and genetic rat models of ADHD: a pilot study.

DasBanerjee Tania T Middleton Frank A FA Berger David F DF Lombardo John P JP Sagvolden Terje T Faraone Stephen V SV

American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 20081201 8

Attention deficit hyperactivity disorder (ADHD) is the most common neurobehavioral disorder in school-aged children. In addition to genetic factors, environmental influences or gene x 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 ...[more]

PMID: 18937310

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Project description:ADHD is the most common neurobehavioral disorder in school-aged children. In addition to genetic factors, environmental influences or gene x 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. 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.

Project description:Background: Topographic memory is the ability to reach various places by recognizing spatial layouts and getting oriented in familiar environments. It involves several different cognitive abilities, in particular executive functions (EF), such as attention, working memory, and planning. Children with attention deficit hyperactivity disorder (ADHD) show impairments in inhibitory control, regulation of attention, planning, and working memory. Aim: The aim of this study was to evaluate the topographic memory in children with ADHD-combined subtype (ADHD-C). Method: Fifteen children (8-10 years) with a diagnosis of ADHD-C (DSM-5) (ADHD-C group) were compared to 15 children with typical development (TD group) of the same age. All children performed Raven's colored progressive matrices (CPM) test to obtain a measure related with cognitive functioning. The walking Corsi test (WalCT), a large-scale version of the Corsi block-tapping test, was used to assess topographic memory in experimental environment. Results: A higher impairment was observed in ADHD-C than TD with significant differences in the WalCT, in particular on the topographic short-term memory (TSTM) task, on the topographic learning (TL) task, and on the repetition number (RN) task during the TL task. Perseverative errors were reported in performing the square-sequence in the WalCT. Zero-order correlations showed a positive correlation between TSTM and auditory attention, and memory of design of NEPSY-II and digit span of WISC-IV. No statistically significant differences were found between the ADHD-C group and TD group in the TL task in the WalCT condition. Conclusion: In ADHD-C, initial topographic learning was compromised whereas the long-term retention of learned topographical material seemed to not be impaired. In particular, these impairments seem to be linked with difficulties in sustained attention, in spatial memory for novel visual materials, in a poor working memory, and in perseverative behaviors.

Dataset Information

A comparison of molecular alterations in environmental and genetic rat models of ADHD: a pilot study.

Publications

A comparison of molecular alterations in environmental and genetic rat models of ADHD: a pilot study.

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