1. Miyake K, Hirasawa T, Soutome M, Itoh M, Goto YI, Endoh K, Takahashi K, Kudo S, Nakagawa T, Yokoi S, Taira T, Inazawa J, Kubota T. {{The protocadherins, PCDHB1 and PCDH7, are regulated by MeCP2 in neuronal cells and brain tissues: Implication for the pathogenesis of Rett syndrome}}. {BMC Neurosci};2011 (Aug 8);12(1):81.
ABSTRACT: BACKGROUND: Rett syndrome is a neurodevelopmental and autistic disease caused by mutations of Methyl-CpG-binding protein 2 (MECP2) gene. MeCP2 protein is mainly expressed in neurons and binds to methylated gene promoters to suppress their expression, indicating that Rett syndrome is caused by the deregulation of target genes in neurons. However, it is likely that there are more unidentified neuronal MeCP2-targets associated with the neurological features of RTT. RESULTS: Using a genome-microarray approach, we found 22 genomic regions that contain sites potentially regulated by MeCP2 based on the features of MeCP2 binding, DNA methylation, and repressive histone modification in human cell lines. Within these regions, Chromatin immunoprecipitation (ChIP) analysis revealed that MeCP2 binds to the upstream regions of the protocadherin genes PCDHB1 and PCDH7 in human neuroblastoma SH-SY5Y cells. PCDHB1 and PCDH7 promoter activities were down-regulated by MeCP2, but not by MBD-deleted MeCP2. These gene expression were up-regulated following MeCP2 reduction with siRNA in SH-SY5Y cells and in the brains of Mecp2-null mice. Furthermore, PCDHB1 was up-regulated in postmortem brains from Rett syndrome patients. CONCLUSIONS: We identified MeCP2 target genes that encode neuronal adhesion molecules using ChIP-on-BAC array approach. Since these protocadherin genes are generally essential for brain development, aberrant regulation of these molecules may contribute to the pathogenesis of the neurological features observed in Rett syndrome.
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2. Pasini A, D’Agati E, Pitzianti M, Casarelli L, Curatolo P. {{Motor examination in children with Attention-Deficit/Hyperactivity Disorder and Asperger Syndrome}}. {Acta Paediatr};2011 (Aug 8)
Aim: Evaluating if motor skills could differentiate drug-naive subjects with two neurodevelopmental disorders: Attention-deficit hyperactivity disorder and Asperger syndrome. Methods: 36 boys (12 with Attention-deficit hyperactivity disorder, 12 with Asperger syndrome, and 12 with typical development) aged 8-12, were evaluated using the Physical and Neurological Examination for Subtle Signs. Three primary outcome variables were obtained: 1) total speed of timed activities, 2) total overflow, and 3) total dysrhythmia. Results: Children with Asperger syndrome performed more slowly than those with Attention-deficit hyperactivity disorder and healthy children independently of age and IQ. Total dysrhythmia differentiates Attention-deficit hyperactivity disorder and Asperger syndrome children from controls. Conclusion: Dysfunction of the fronto-striatal-cerebellar networks related to motor control could be the physiopathological basis of the reported findings.
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3. Wink LK, Erickson CA, Stigler KA, McDougle CJ. {{Riluzole in Autistic Disorder}}. {J Child Adolesc Psychopharmacol};2011 (Aug 8)
