carbocyanines and Autistic-Disorder

Altered brain development during embryogenesis and early postnatal life has been hypothesized to be responsible for the abnormal behaviors of people with autism. The specific genetic background that alters vulnerability to some environmental insults has been suggested in the etiology of autism; however, the specific pathomechanisms have not been identified. Recently, we showed that sera from children with autism alter the maturation of human neuronal progenitor cells (NPCs) in culture. Results suggest that pre-programmed neurogenesis, i.e., neuronal proliferation, migration, differentiation, growth, and circuit organization, can be affected differently by factors present in autistic sera. In this report, we tested the effect of autistic sera on the vulnerability of NPCs to oxidative stress-a recognized risk factor of autism. We found that mild oxidative stress reduced proliferation of differentiating NPCs but not immature NPCs. This decrease of proliferation was less prominent in cultures treated with sera from children with autism than from age-matched controls. These results suggest that altered response of NPCs to oxidative stress may play a role in the etiology of autism.

Topics: Adolescent; Analysis of Variance; Apoptosis; Autistic Disorder; Bromodeoxyuridine; Carbocyanines; Cell Movement; Cell Proliferation; Cells, Cultured; Child; Child, Preschool; Doublecortin Domain Proteins; Embryonic Stem Cells; Female; Ferrous Compounds; Fetus; Humans; Infant; Intermediate Filament Proteins; Male; Microtubule-Associated Proteins; Nerve Tissue Proteins; Nestin; Neurons; Neuropeptides; Oxidative Stress; Phosphopyruvate Hydratase; Serum; SOXB1 Transcription Factors; Time Factors; Tubulin

Single nucleotide polymorphisms (SNPs) are important markers which can be used in association studies searching for susceptible genes of complex diseases. High-throughput methods are needed for SNP genotyping in a large number of samples. In this study, we applied polyacrylamide gel-based microarray combined with dual-color hybridization for association study of four BDNF polymorphisms with autism. All the SNPs in both patients and controls could be analyzed quickly and correctly. Among four SNPs, only C270T polymorphism showed significant differences in the frequency of the allele (chi(2) = 7.809, p = 0.005) and genotype (chi(2) = 7.800, p = 0.020). In the haplotype association analysis, there was significant difference in global haplotype distribution between the groups (chi(2) = 28.19, p = 3.44e-005). We suggest that BDNF has a possible role in the pathogenesis of autism. The study also show that the polyacrylamide gel-based microarray combined with dual-color hybridization is a rapid, simple and high-throughput method for SNPs genotyping, and can be used for association study of susceptible gene with disorders in large samples.

Topics: Alleles; Autistic Disorder; Brain-Derived Neurotrophic Factor; Carbocyanines; Child; Child, Preschool; Electrophoresis, Gel, Pulsed-Field; Female; Fluorescent Dyes; Genetic Association Studies; Genotype; Haplotypes; Humans; Male; Oligonucleotide Array Sequence Analysis; Polymorphism, Single Nucleotide