Rat Models of ADHD

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DRD4 and DAT1 in ADHD: functional neurobiology to pharmacogenetics

Attention deficit/hyperactivity disorder (ADHD) is a common and potentially very impairing neuropsychiatric disorder of childhood. Statistical genetic studies of twins have shown ADHD to be highly heritable, with the combination of genes and gene by environment interactions accounting for around 80% of phenotypic variance. The initial molecular genetic studies where candidates were selected because of the efficacy of dopaminergic compounds in the treatment of ADHD were remarkably successful and provided strong evidence for the role of DRD4 and DAT1 variants in the pathogenesis of ADHD. However, the recent application of noncandidate gene strategies (eg, genome-wide association scans) has failed to identify additional genes with substantial genetic main effects, and the effects for DRD4 and DAT1 have not been replicated. This is the usual pattern observed for most other physical and mental disorders evaluated with current state-of-the-art methods. In this paper we discuss future strategies for genetic studies in ADHD, highlighting both the pitfalls and possible solutions relating to candidate gene studies, genome-wide studies, defining the phenotype, and statistical approaches

A functional polymorphism in the succinate-semialdehyde dehydrogenase (aldehyde dehydrogenase 5 family, member A1) gene is associated with cognitive ability

Succinate-semialdehyde dehydrogenase (SSADH) deficiency is a rare cause of learning disability. We have investigated SSADH to assess its contribution to cognitive ability in the general population in both case–control- and family-based analyses. Sequence analysis of SSADH revealed four changes affecting the encoded protein, only one of which had a minor allele whose frequency is even moderately common. We genotyped this functional polymorphism in 197 high-IQ cases, 201 average-IQ controls and 196 parent high-IQ offspring trios. The minor allele was significantly less frequent in high-IQ cases and was significantly less frequently transmitted by parents to high-IQ subjects than chance expectation. A previous study has shown that the minor allele encodes a lower activity enzyme than the major allele. These data suggest that higher SSADH activity is associated with higher intelligence across the general population. The effect is small, with each allele having an effect size translating to about 1.5 IQ point

No association between apolipoprotein E polymorphisms and general cognitive ability in children

In this work we explored the hypothesis that variation in the gene encoding apolipoprotein E (ApoE) is a factor modifying general cognitive ability (g). A case control sample of 101 high g and 101 average g children was scored for ApoE genotypes and two variants in the transcriptional regulatory region of the gene (Th1/E47cs and -491 AT). No evidence of association between these polymorphisms and g was found. We conclude that variation at these loci is not a factor with a measurable impact on general cognitive ability in the healthy population

Evaluation of the efficacy of supplementing breeding calves with injectables copper

La hipocuprosis bovina es una de las principales enfermedades que afectan al ganado en pastoreo en argentina.Posee una clara incidencia geográfica, siendo la cuenca deprimida del Río del Salado donde adquiere mayor importancia. Durante la deficiencia se produce la alteración del funcionamiento de numerosas cupro-enzimas, fenómeno que se vincula con la aparición de los signos clínicos y subclínicos de la enfermedad. El objetivo del presente trabajo fue evaluar el valor terapéutico de un modelo de suplementación estratégica con cobre en terneros, consistente en una única suplementación al promediar los 4-5 meses de edad.Se estudiaron 3 grupos de 20 animales. El primero, bajo suplementación continua (control +), el segundo sin suplementación (control -), y finalmente el grupo en estudio, al cual se le aplicó una sola dosis en diciembre. Se realizaron 4 muestreos y en cada uno se analizó la cupremia, la ganancia diaria de peso y la evolución de los pesos.Los resultados obtenidos permitieron demostrar que una única dosis de Cu permitio mantener hasta 2 meses los niveles de normocupremia y evitaron una posterior hipocupremia severa. Las ganancias de peso no permitieron una diferenciación estadística, pero si marcaron una tendencia hacia una mayor ganancia de peso asociada con la suplementación.Fil: Mattioli, Guillermo Alberto. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Laboratorio de Nutrición Mineral, Cátedra de Fisiología; ArgentinaFil: Fazzio, Luis Emilio. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Laboratorio de Nutrición Mineral, Cátedra de Fisiología; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Cátedra de Clínica de Grandes Animales; ArgentinaFil: Rosa, D.E.. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Laboratorio de Nutrición Mineral, Cátedra de Fisiología; ArgentinaFil: Picco, Sebastian Julio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Laboratorio de Nutrición Mineral, Cátedra de Fisiología; ArgentinaFil: Angelico, D.. Biogénesis Bagó. Investigación y Desarrollo ; ArgentinaFil: Turic, E.. Biogénesis Bagó. Investigación y Desarrollo; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Laboratorio de Nutrición Mineral, Cátedra de Fisiología; Argentin