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Comparative Study
. 2008 Dec 5;147B(8):1554-63.
doi: 10.1002/ajmg.b.30877.

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

Tania DasBanerjee  1 , Frank A Middleton, David F Berger, John P Lombardo, Terje Sagvolden, Stephen V Faraone
Affiliations
Comparative Study

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

Tania DasBanerjee et al. Am J Med Genet B Neuropsychiatr Genet. .

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.

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References

    1. Abdolmaleky HM, Cheng KH, Faraone SV, Wilcox M, Glatt SJ, Gao F, Smith CL, Shafa R, Aeali B, Carnevale J, et al. Hypomethylation of MB-COMT promoter is a major risk factor for schizophrenia and bipolar disorder. Hum Mol Genet. 2006;15(21):3132–45. - PMC - PubMed
    1. Akiyama K, Yabe K, Sutoo D. Quantitative immunohistochemical distributions of tyrosine hydroxylase and calmodulin in the brains of spontaneously hypertensive rats. Kitasato Arch Exp Med. 1992;65(4):199–208. - PubMed
    1. Alexander GE, DeLong MR, Strick PL. Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci. 1986;9:357–81. - PubMed
    1. Angus WG, Mousa MA, Vargas VM, Quensen JF, Boyd SA, Contreras ML. Inhibition of L-aromatic amino acid decarboxylase by polychlorinated biphenyls. Neurotoxicology. 1997;18(3):857–67. - PubMed
    1. Banerjee TD, Middleton F, Faraone SV. Environmental risk factors for attention-deficit hyperactivity disorder. Acta Paediatr. 2007;96(9):1269–74. - PubMed

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