1. Alhowikan AM. {{Activity-Regulated Cytoskeleton-Associated Protein Dysfunction May Contribute to Memory Disorder and Earlier Detection of Autism Spectrum Disorders}}. {Med Princ Pract};2016 (Mar 11)
OBJECTIVE: To explore a possible role for activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) in the clinical identification of children with autism. SUBJECTS AND METHODS: The plasma levels of Arc/Arg3.1 in 62 boys with autism and 32 healthy boys were measured using enzyme-linked immunosorbent assay (ELISA). The Childhood Autism Rating Scale (CARS) was used to assess severity of autism as defined in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, (DSM-IV). Mann-Whitney U tests were used for comparisons between children with autism and healthy children. Spearman’s r correlation coefficient (r) was used to determine the relationship between the CARS scores among patients with autism and different variables. RESULTS: The mean plasma level of Arc/Arg3.1 protein in autism was 1.689 +/- 0.917 pg/mL, significantly higher than that of healthy controls: 0.792 +/- 1.056 pg/mL (p < 0.001). No significant relationship was found between plasma levels of Arc/Arg3.1 protein and CARS scores (r = - 0.06; p > 0.05), age (r = – 0.27; p > 0.05). CONCLUSIONS: The mean plasma level of Arc/Arg3.1 protein was higher in children with autism than in controls, suggesting that Arc/Arg3.1 could be a potential early blood biomarker for diagnosis of autism.
.
Lien vers le texte intégral (Open Access ou abonnement)
2. Azad GF, Locke J, Kasari C, Mandell DS. {{Race, disability, and grade: Social relationships in children with autism spectrum disorders}}. {Autism};2016 (Mar 10)
Race is associated with social relationships among typically developing children; however, studies rarely examine the impact of race on social outcomes for children with autism spectrum disorder. This study examined how race (African American, Latino, Asian, or White) in conjunction with disability status (autism spectrum disorders or typically developing) and grade (grades K-2 or 3-5) affects friendships and social networks. The sample comprises 85 children with autism spectrum disorders and 85 typically developing controls matched on race, gender, age/grade, and classroom (wherever possible). Race, disability, and grade each had an independent effect on friendship nominations, and there was an interaction among the three variables. Specifically, children with autism spectrum disorders who were African American or Latino in the upper elementary grades received fewer friendship nominations than typically developing White children in the lower elementary grades. Only the presence of autism spectrum disorders was associated with social network centrality. Our results also suggested that Latino children with autism spectrum disorders in the upper elementary grades were at the highest risk of social isolation. Implications for re-conceptualizing social skills interventions are discussed.
Lien vers le texte intégral (Open Access ou abonnement)
3. Burbach JP. {{AUTISM. Unraveling a pathway to autism}}. {Science};2016 (Mar 11);351(6278):1153-1154.
Lien vers le texte intégral (Open Access ou abonnement)
4. Dioguardi CC, Uslu B, Haynes M, Kurus M, Gul M, Miao DQ, De Santis L, Ferrari M, Bellone S, Santin A, Giulivi C, Hoffman G, Usdin K, Johnson J. {{Granulosa Cell and Oocyte Mitochondrial Abnormalities in a Mouse Model of Fragile X Primary Ovarian Insufficiency}}. {Mol Hum Reprod};2016 (Mar 9)
STUDY HYPOTHESIS: We hypothesized that the mitochondria of granulosa cells (GC) and/or oocytes might be abnormal in a mouse model of Fragile X premutation (FXPM). STUDY FINDING: Mice heterozygous and homozygous for the FXPM have increased death (atresia) of large ovarian follicles, fewer corpora lutea with a gene dosage effect manifesting in decreased litter size(s). Furthermore, granulosa cells (GC) and oocytes of FXPM mice have decreased mitochondrial content, structurally abnormal mitochondria, and reduced expression of critical mitochondrial genes. Because this mouse allele produces the mutant Fragile x mental retardation 1 (Fmr1) transcript and reduced levels of wild-type (WT) Fmr1 protein (FMRP), but does not produce a Repeat Associated Non-ATG Translation (RAN)-translation product, our data lend support to the idea that Fmr1 mRNA with large numbers of CGG-repeats is intrinsically deleterious in the ovary.What is known already: Mitochondrial dysfunction has been detected in somatic cells of human and mouse FX PM carriers and mitochondria are essential for oogenesis and ovarian follicle development, FX-associated primary ovarian insufficiency (FXPOI) is seen in women with FXPM alleles. These alleles have 55-200 CGG repeats in the 5′ UTR of an X-linked gene known as FMR1. The molecular basis of the pathology seen in this disorder is unclear but is thought to involve either some deleterious consequence of overexpression of RNA with long CGG-repeat tracts or of the generation of a repeat-associated non-AUG translation (RAN translation) product that is toxic. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: Analysis of ovarian function in a knock-in FXPM mouse model carrying 130 CGG repeats was performed as follows on WT, PM/+, and PM/PM genotypes. Histomorphometric assessment of follicle and corpora lutea numbers in ovaries from 8-month-old mice was executed, along with litter size analysis. Mitochondrial DNA copy number was quantified in oocytes and GC using quantitative PCR, and cumulus granulosa mitochondrial content was measured by flow cytometric analysis after staining of cells with Mitotracker dye. Transmission electron micrographs were prepared of GC within small growing follicles and mitochondrial architecture was compared. Quantitative RT-PCR analysis of key genes involved in mitochondrial structure and recycling was performed. MAIN RESULTS AND THE ROLE OF CHANCE: A defect was found in follicle survival at the large antral stage in PM/+ and PM/PM mice. Litter size was significantly decreased in PM/PM mice, and corpora lutea were significantly reduced in mice of both mutant genotypes. Mitochondrial DNA copy number was significantly decreased in GC and metaphase II eggs in mutants. Flow cytometric analysis revealed that PM/+ and PM/PM animals lack the cumulus GC that harbor the greatest mitochondrial content as found in wild-type animals. Electron microscopic evaluation of GC of small growing follicles revealed mitochondrial structural abnormalities, including disorganized and vacuolar cristae. Finally, aberrant mitochondrial gene expression was detected. Mitofusin 2 (Mfn2) and Optic atrophy 1 (Opa1), genes involved in mitochondrial fusion and structure, respectively, were significantly decreased in whole ovaries of both mutant genotypes. Mitochondrial fission factor 1 (Mff1) was significantly decreased in PM/+ and PM/PM GC and eggs compared to wild-type controls. LIMITATIONS, REASONS FOR CAUTION: Data from the mouse model used for these studies should be viewed with some caution when considering parallels to the human FXPOI condition. WIDER IMPLICATIONS OF THE FINDINGS: Our data lend support to the idea that Fmr1 mRNA with large numbers of CGG-repeats is intrinsically deleterious in the ovary. FXPM disease states, including FXPOI, may share mitochondrial dysfunction as a common underlying mechanism.Large scale data: Not applicable. STUDY FUNDING AND COMPETING INTERESTS: Studies were supported by NIH R21 071873 (J.J./G.H), The Albert McKern Fund for Perinatal Research (J.J.), NIH Intramural Funds (K.U.), and a TUBITAK Research Fellowship Award (B.U.). No conflict(s) of interest or competing interest(s) are noted.
Lien vers le texte intégral (Open Access ou abonnement)
5. Li Q, Zhou JM. {{The microbiota-gut-brain axis and its potential therapeutic role in autism spectrum disorder}}. {Neuroscience};2016 (Mar 7)
Autism spectrum disorder (ASD) is a series of neurodevelopmental disorders that are characterized by deficits in both social and cognitive functions. Although the exact etiology and pathology of ASD remain unclear, a disorder of the microbiota-gut-brain axis is emerging as a prominent factor in the generation of autistic behaviors. Clinical studies have shown that gastrointestinal symptoms and compositional changes in the gut microbiota frequently accompany cerebral disorders in patients with ASD. A disturbance in the gut microbiota, which is usually induced by a bacterial infection or chronic antibiotic exposure, has been implicated as a potential contributor to ASD. The bidirectional microbiota-gut-brain axis acts mainly through neuroendocrine, neuroimmune, and autonomic nervous mechanisms. Application of modulators of the microbiota-gut-brain axis, such as probiotics, helminthes and certain special diets, may be a promising strategy for the treatment of ASD. This review mainly discusses the salient observations of the disruptions of the microbiota-gut-brain axis in the pathogenesis of ASD and reveals its potential therapeutic role in autistic deficits.
Lien vers le texte intégral (Open Access ou abonnement)
6. Neely-Barnes SL, Elswick SE. {{Inclusion for People with Developmental Disabilities: Measuring an Elusive Construct}}. {J Soc Work Disabil Rehabil};2016 (Mar 11)
The philosophy of inclusion for people with intellectual and developmental disabilities (IDD) has evolved over the last fifty years. Over time, inclusion research has shifted from a focus on deinstitutionalization to understanding the extent to which individuals with IDD are meaningfully involved in the community and social relationships. Yet, there has been no agreed upon way to measure inclusion. Many different measurement and data collection techniques have been used in the literature. The present study proposes a brief measure of inclusion that can be used with family members and on survey instruments.
Lien vers le texte intégral (Open Access ou abonnement)
7. Shtayermman O. {{Fred R. Volkmar; Sally J. Rogers, Rhea Paul; Kevin A. Pelphery: Handbook of Autism and Pervasive Developmental Disorders : 4th Edition, Volume 1 and 2, John Wiley and Sons, Inc, 2014, 1312 pp, ISBN: 978-1-118-14068-0, $300.00 (hardcover)}}. {J Autism Dev Disord};2016 (Mar 12)
Lien vers le texte intégral (Open Access ou abonnement)
8. Yi F, Danko T, Botelho SC, Patzke C, Pak C, Wernig M, Sudhof TC. {{Autism-associated SHANK3 haploinsufficiency causes Ih channelopathy in human neurons}}. {Science};2016 (Mar 10)
Heterozygous SHANK3 mutations are associated with idiopathic autism and Phelan-McDermid syndrome. SHANK3 is a ubiquitously expressed scaffolding protein that is enriched in postsynaptic excitatory synapses. Here, we used engineered conditional mutations in human neurons and found that heterozygous and homozygous SHANK3 mutations severely and specifically impaired Ih channels. SHANK3 mutations caused alterations in neuronal morphology and synaptic connectivity; chronic pharmacological blockage of Ih channels reproduced these phenotypes, suggesting that they may be secondary to Ih-channel impairment. Moreover, mouse Shank3-deficient neurons also exhibited severe decreases in Ih currents. SHANK3 protein interacted with hyperpolarization-activated cyclic nucleotide-gated channel proteins (HCN proteins) forming Ih channels, indicating that SHANK3 functions to organize HCN channels. Our data suggest SHANK3 mutations predispose to autism, at least partially, by inducing an Ih channelopathy that may be amenable to pharmacological intervention.
