1. Chauhan A, Gu F, Essa MM, Wegiel J, Kaur K, Ted Brown W, Chauhan V. {{Brain region-specific deficit in mitochondrial electron transport chain complexes in children with autism}}. {J Neurochem};2011 (Jan 19)
Mitochondria play important roles in generation of free radicals, ATP formation, and in apoptosis. We studied the levels of mitochondrial electron transport chain (ETC) complexes, i.e., complexes I, II, III, IV, and V, in brain tissue samples from the cerebellum and the frontal, parietal, occipital, and temporal cortices of subjects with autism and age-matched control subjects. The subjects were divided into two groups according to their ages: Group A (children, ages 4-10 years) and Group B (adults, ages 14-39 years). In Group A, we observed significantly lower levels of complexes III and V in the cerebellum (p < 0.05), of complex I in the frontal cortex (p < 0.05), and of complexes II (p < 0.01), III (p < 0.01), and V (p < 0.05) in the temporal cortex of children with autism as compared to age-matched control subjects, while none of the five ETC complexes was affected in the parietal and occipital cortices in subjects with autism. In the cerebellum and temporal cortex, no overlap was observed in the levels of these ETC complexes between subjects with autism and control subjects. In the frontal cortex of Group A, a lower level of ETC complexes was observed in a subset of autism cases, i.e., 60% (3/5) for complexes I, II, and V, and 40% (2/5) for complexes III and IV. A striking observation was that the levels of ETC complexes were similar in adult subjects with autism and control subjects (Group B). A significant increase in the levels of lipid hydroperoxides, an oxidative stress marker, was also observed in the cerebellum and temporal cortex in the children with autism. These results suggest that the expression of ETC complexes is decreased in the cerebellum and the frontal and temporal regions of the brain in children with autism, which may lead to abnormal energy metabolism and oxidative stress. The deficits observed in the levels of ETC complexes in children with autism may readjust to normal levels by adulthood.
2. O’Hearn K, Lakusta L, Schroer E, Minshew N, Luna B. {{Deficits in adults with autism spectrum disorders when processing multiple objects in dynamic scenes}}. {Autism Res};2011 (Jan 19)
People with autism spectrum disorders (ASD) process visual information in a manner that is distinct from typically developing individuals. They may be less sensitive to people’s goals and, more generally, focus on visual details instead of the entire scene. To examine these differences, people with and without ASD were asked to detect changes in dynamic scenes with multiple elements. Participants viewed a brief video of a person or an inanimate object (the « figure ») moving from one object to another; after a delay, they reported whether a second video was the same or different. Possible changes included the figure, the object the figure was moving from, or the object the figure was moving toward (the « goal »). We hypothesized that individuals with ASD would be less sensitive to changes in scenes with people, particularly elements that might be the person’s goal. Alternately, people with ASD might attend to fewer elements regardless of whether the scene included a person. Our results indicate that, like controls, people with ASD noticed a change in the « goal » object at the end of a person’s movement more often than the object at the start. However, the group with ASD did not undergo the developmental improvement that was evident typically when detecting changes in both the start and end objects. This atypical development led to deficits in adults with ASD that were not specific to scenes with people or to « goals. » Improvements in visual processing that underlie mature representation of scenes may not occur in ASD, suggesting that late developing brain processes are affected.
3. Wintle RF, Lionel AC, Hu P, Ginsberg SD, Pinto D, Thiruvahindrapduram B, Wei J, Marshall CR, Pickett J, Cook EH, Scherer SW. {{A genotype resource for postmortem brain samples from the autism tissue program}}. {Autism Res};2011 (Jan 19)
The Autism Tissue Program (ATP), a science program of Autism Speaks, provides researchers with access to well-characterized postmortem brain tissues. Researchers access these tissues through a peer-reviewed, project-based approval process, and obtain related clinical information from a secure, online informatics portal. However, few of these samples have DNA banked from other sources (such as a blood sample from the same individual), hindering genotype-phenotype correlation and interpretation of gene expression data derived from the banked brain tissue. Here, we describe an initiative to extract DNA from Brodmann Area 19, and genotype these samples using both the Affymetrix Genome-Wide Human SNP Array 6.0 and the Illumina Human1M-Duo DNA Analysis BeadChip genome-wide microarray technologies. We additionally verify reported gender, and infer ethnic background from the single nucleotide polymorphism data. We have also used a rigorous, multiple algorithm approach to identify genomic copy number variation (CNV) from these array data. Following an initial proof of principle study using two samples, 52 experimental samples, consisting of 27 subjects with confirmed or suspected autism and related disorders, 5 subjects with cytogenetically visible duplications of 15q, 2 with epilepsy and 18 age-matched normal controls were processed, yielding high-quality genotype data in all cases. The genotype and CNV data are provided via the ATP informatics portal as a resource for the autism research community.
