A Comparison of Molecular Alterations in Environmental and Genetic Rat Models of ADHD: a pilot study
Tania DasBanerjee,Frank A. Middleton,Frank A. Middleton,David F. Berger,John P. Lombardo,Terje Sagvolden,Stephen V. Faraone,Stephen V. Faraone +7 more
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TLDR
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.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.read more
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Journal ArticleDOI
Molecular genetics of attention deficit hyperactivity disorder.
Stephen V. Faraone,Eric Mick +1 more
TL;DR: Although twin studies demonstrate that ADHD is a highly heritable condition, molecular genetic studies suggest that the genetic architecture of ADHD is complex as discussed by the authors, and the handful of genomewide linkage and association scans that have been conducted thus far show divergent findings and are therefore not conclusive.
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Genome-wide copy number variation study associates metabotropic glutamate receptor gene networks with attention deficit hyperactivity disorder
Josephine Elia,Joseph T. Glessner,Kai Wang,Nagahide Takahashi,Corina Shtir,Dexter Hadley,Patrick M. A. Sleiman,Haitao Zhang,Cecilia E. Kim,Reid J. Robison,Gholson J. Lyon,James H. Flory,Jonathan P. Bradfield,Marcin Imielinski,Cuiping Hou,Edward C. Frackelton,Rosetta M. Chiavacci,Takeshi Sakurai,Cara R. Rabin,Frank A. Middleton,Kelly A. Thomas,Maria Garris,Frank D. Mentch,Christine M. Freitag,Hans-Christoph Steinhausen,Hans-Christoph Steinhausen,Hans-Christoph Steinhausen,Alexandre A. Todorov,Andreas Reif,Aribert Rothenberger,Barbara Franke,Eric Mick,Herbert Roeyers,Jan K. Buitelaar,Klaus-Peter Lesch,Tobias Banaschewski,Richard P. Ebstein,Fernando Mulas,Robert D. Oades,Joseph A. Sergeant,Edmund J.S. Sonuga-Barke,Edmund J.S. Sonuga-Barke,Edmund J.S. Sonuga-Barke,Tobias J. Renner,Marcel Romanos,Jasmin Romanos,Andreas Warnke,Susanne Walitza,Susanne Walitza,Jobst Meyer,Haukur Palmason,Christiane Seitz,Sandra K. Loo,Susan L. Smalley,Joseph Biederman,Lindsey Kent,Philip Asherson,Richard Anney,J. William Gaynor,Philip Shaw,Marcella Devoto,Peter White,Struan F.A. Grant,Struan F.A. Grant,Joseph D. Buxbaum,Judith L. Rapoport,Nigel Williams,Stanley F. Nelson,Stephen V. Faraone,Hakon Hakonarson +69 more
TL;DR: A gene network analysis showed that genes interacting with the genes in the GRM family are enriched for CNVs in ∼10% of the cases, and rare recurrent CNVs affecting glutamatergic neurotransmission genes that were overrepresented in multiple ADHD cohorts were identified.
Journal ArticleDOI
Mutations in GNAL cause primary torsion dystonia.
Tania Fuchs,Rachel Saunders-Pullman,Rachel Saunders-Pullman,Ikuo Masuho,Marta San Luciano,Deborah Raymond,Stewart A. Factor,Anthony E. Lang,Tsao-Wei Liang,Richard Trosch,Sierra R. White,E Ainehsazan,Denis Hervé,Denis Hervé,Nutan Sharma,Michelle E. Ehrlich,Kirill A. Martemyanov,Susan B. Bressman,Susan B. Bressman,Laurie J. Ozelius +19 more
TL;DR: Using exome sequencing in two families with PTD, a new causative gene, GNAL, is identified with a nonsense mutation encoding p.Ser293* resulting in a premature stop codon in one family and a missense mutation encode p.Val137Met in the other.
Journal ArticleDOI
Owner reports of attention, activity, and impulsivity in dogs: a replication study
TL;DR: Reliability analyses confirmed two scales previously identified for dogs (inattention [IA], hyperactivity-impulsivity [HA-IM]).
Journal ArticleDOI
The Spontaneously Hypertensive Rat model of ADHD – the importance of selecting the appropriate reference strain
Terje Sagvolden,Espen Borgå Johansen,Grete Wøien,S. Ivar Walaas,Jon Storm-Mathisen,Linda H. Bergersen,Øivind Hvalby,Vidar Jensen,Heidi Aase,Vivienne A. Russell,Peter R. Killeen,Tania DasBanerjee,Frank A. Middleton,Stephen V. Faraone +13 more
TL;DR: It is argued that WKY rats obtained from Charles River, Germany (WKY/NCrl) provide a promising model for the predominantly inattentive subtype of ADHD (ADHD-PI); in this case also the WKY/NHsd substrain should be used as control.
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