Modeling hyperactivity: Of mice and men

Nature medicine (Impact Factor: 27.36). 05/2011; 17(5):541-2. DOI: 10.1038/nm0511-541
Source: PubMed
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    ABSTRACT: Attention-deficit hyperactivity disorder (ADHD) is one of the most common psychiatric disorders in children with a worldwide prevalence of 5.3%. Recently, a Korean group assessed the G-protein-coupled receptor kinase-interacting protein 1 (GIT1) gene that had previously been associated with ADHD. In their work, 27 single nucleotide polymorphisms SNPs in the GIT1 gene were tested; however, only the rs550818 SNP was associated with ADHD susceptibility. Moreover, the presence of the risk-associated allele determined reduced GIT1 expression, and Git1-deficient mice exhibit ADHD-like phenotypes. The aim of this study was to determine if this association also occurs in a sample of Brazilian children with ADHD. No effect of GIT1 genotypes on ADHD susceptibility was observed in the case-control analysis. The odds ratios (ORs) were 0.75 (P = 0.184) for the CT genotype and 1.09 (P = 0.862) for the TT genotype. In addition, the adjusted OR of the CT+TT genotypes vs. the CC genotype was also estimated (P = 0.245). There were no dimensional associations between the GIT1 genotypes and both hyperactivity and /impulsivity, and only hyperactivity Swanson, Nolan and Pelham Scale-Version IV (SNAP-IV) scores (P = 0.609 and P = 0.247, respectively). The transmission/disequilibrium test indicated that there was no over-transmission of rs550818 alleles from parents to ADHD children (z = 0.305; P = 0.761). We conclude that rs550818 is not associated with ADHD in this Brazilian sample. More studies are required before concluding that this polymorphism plays a role in ADHD susceptibility.
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    ABSTRACT: Mutant mice have been used successfully as a tool for investigating the mechanisms of memory at multiple levels, from genes to behavior. In most cases, manipulating a gene expressed in the brain impairs cognitive functions such as memory and their underlying cellular mechanisms, including synaptic plasticity. However, a remarkable number of mutations have been shown to enhance memory in mice. Understanding how to improve a system provides valuable insights into how the system works under normal conditions, because this involves understanding what the crucial components are. Therefore, more can be learned about the basic mechanisms of memory by studying mutant mice with enhanced memory. This review will summarize the genes and signaling pathways that are altered in the mutants with enhanced memory, as well as their roles in synaptic plasticity. Finally, I will discuss how knowledge of memory-enhancing mechanisms could be used to develop treatments for cognitive disorders associated with impaired plasticity.
    Molecular Brain 06/2014; 7(1):43. DOI:10.1186/1756-6606-7-43 · 4.90 Impact Factor