1. Ahmad SF, Ansari MA, Nadeem A, Bakheet SA, Alsanea S, Al-Hosaini KA, Mahmood HM, Alzahrani MZ, Attia SM. {{Inhibition of tyrosine kinase signaling by tyrphostin AG126 downregulates the IL-21/IL-21R and JAK/STAT pathway in the BTBR mouse model of autism}}. {Neurotoxicology};2019 (Dec 4)
Autism spectrum disorder (ASD) comprises a broad range of neurodevelopmental disorders that are associated with deficits in social interaction and communication. The tyrosine kinase inhibitor tyrphostin AG126 represents a promising therapeutic agent for several neuroinflammatory disorders. There are currently no treatments available that can improve ASD and we previously showed that AG126 treatment exerts beneficial effects on BTBR T(+) Itpr3(tf)/J (BTBR) mice, a model for autism that shows the core features of ASD; however, the immunological mechanisms and molecular targets associated with this effect were previously unclear. This study was undertaken to delineate the neuroprotective effect of AG126 on BTBR mice. Here, using this mouse model, we investigated the effects of AG126 administration on IL-21R, IL-21, IL-22, TNF-alpha, NOS2, STAT3, IL-27, and Foxp3 production by CD8(+) T cells in the spleen by flow cytometry. We further explored the mRNA and protein expression of IL-21, IL-22, IL-1beta, TNF-alpha, NOS2, JAK1, STAT3, IL-27, and Foxp3 in brain tissue by RT-PCR, and western blotting. We found that BTBR mice treated with AG126 exhibited significant decreases in IL-21R-, IL-21-, IL-22-, TNF-alpha-, NOS2-, STAT3-producing, and increases in IL-27- and Foxp3-producing, CD8(+) T cells. Our results further demonstrated that AG126 treatment effectively decreased IL-21, IL-22, IL-1beta, TNF-alpha, NOS2, JAK1, and STAT3, and increased IL-27 and Foxp3 mRNA and protein expression in brain tissues. Our findings suggest that AG126 elicits a neuroprotective response through downregulation of the IL-21/IL-21R and JAK/STAT pathway in BTBR mice, which could represent a promising novel therapeutic target for ASD treatment.
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2. Cook IA, Wilson AC, Peters JM, Goyal MN, Bebin EM, Northrup H, Krueger D, Leuchter AF, Sahin M. {{EEG Spectral Features in Sleep of Autism Spectrum Disorders in Children with Tuberous Sclerosis Complex}}. {J Autism Dev Disord};2019 (Dec 6)
Tuberous sclerosis complex (TSC) is a multisystem disorder with increased prevalence of autism spectrum disorders (ASDs). This project aimed to characterize the autism phenotype of TSC and identify biomarkers of risk for ASD. Because abnormalities of EEG during sleep are tied to neurodevelopment in children, we compared electroencephalographic (EEG) measures during Stage II sleep in TSC children who either did (ASD+) or did not (ASD-) exhibit symptoms of ASD over 36-month follow up. Relative alpha band power was significantly elevated in the ASD+ group at 24 months of age with smaller differences at younger ages, suggesting this may arise from differences in brain development. These findings suggest that EEG features could enhance the detection of risk for ASD.
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3. Friedrich RE, Kohlrusch FK, Luebke AM. {{Symptomatic Mandibular Fibrous Dysplasia With Concurrent Triple X- and Premutation Stage Fragile-X-Syndrome: Case Report With Short Literature Survey}}. {Anticancer Res};2019 (Dec);39(12):6769-6780.
BACKGROUND: Certain constitutive chromosomal abnormalities of the human X chromosome are relatively common in conspicuous neuropsychiatric findings. Although tumors or tumor-like lesions are occasionally reported in diseases of the X chromosome, they are numerically negligible, for example, in aneuploidy such as the triple X syndrome (TXS). CASE REPORT: A 16-year-old female patient with a known TXS and premutation stage of fragile X syndrome was referred by her dentist for diagnosis and treatment of unilateral cheek swelling. The examination of the psychologically conspicuous patient revealed a unilateral mandibular tumor with dysesthesia of the mental nerve. Surgical removal of soft, crumbly spongiosa over the nerve canal resulted in sufficient pressure release of the constricted nerve and restoration of epicritic sensitivity. Imaging findings and histological and molecular genetic examination revealed monostotic craniofacial fibrous dysplasia. CONCLUSION: Although the data in the literature do not give reason to suppose an accumulation of neoplasms in TXS, a numb chin syndrome should be a reason for detailed diagnostics. Careful diagnosis allows for customized therapy. This is the first report on the coincidence of TXS, fragile X syndrome, and fibrous dysplasia in a single individual.
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4. Harrison AJ, Slane MM. {{Examining How Types of Object Distractors Distinctly Compete for Facial Attention in Autism Spectrum Disorder Using Eye Tracking}}. {J Autism Dev Disord};2019 (Dec 6)
Social motivation theory states that individuals with ASD find social stimuli less rewarding (Chevallier et al. in Trends Cognit Sci 16(4):231-239, 2012). An alternative theory suggests that competition from circumscribed interests (CIs) may better account for diminished social attention (Sasson et al. in Autism Res 1(1):31-42, 2008). This study evaluated both theories in children diagnosed with ASD (n = 16) and a group of TD children (n = 20) using eye tracking and demonstrated that distractor type only impacted the proportion of dwell time on faces in the TD group, but not the ASD group. These results provide support for the social motivation theory because gaze duration for faces among children with ASD was diminished regardless of whether the non-social stimuli presented was a CI or control object.
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5. Holloway CA, Munro N, Jackson J, Phillips S, Ropar D. {{Exploring the autistic and police perspectives of the custody process through a participative walkthrough}}. {Res Dev Disabil};2019 (Dec 4);97:103545.
BACKGROUND: Research suggests that autistic individuals may be more likely to come into contact with police and have more negative experiences in police custody. However, limited information about the difficulties they experience during the custody process is available. AIMS: This study explores the experiences of autistic individuals and officers during a walkthrough of the custody process to identify specific difficulties in these encounters and what support is needed to overcome these. METHODS AND PROCEDURES: A participative walkthrough method was developed to provide autistic individuals and officers an interactive opportunity to identify areas where further support in the custody process was needed. Two autistic participants and three officers took part in the study. OUTCOMES AND RESULTS: Autistic participants reported negative experiences due to: i) the emotional impact of the physical setting and custody process ii) communication barriers leading to increased anxiety and iii) exposure to sensory demands. Officers highlighted three factors which limit their ability to support autistic individuals effectively: i) the custody context ii) barriers to communication and iii) knowledge and understanding of autism. CONCLUSIONS AND IMPLICATIONS: Adjustments are needed to the custody process and environment to support interactions between autistic individuals and officers and improve the overall wellbeing of autistic individuals.
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6. Pan PY, Tammimies K, Bolte S. {{The Association Between Somatic Health, Autism Spectrum Disorder, and Autistic Traits}}. {Behav Genet};2019 (Dec 6)
This study used a twin cohort to investigate the association of autism spectrum disorder (ASD) and autistic traits with somatic health. A total of 344 twins (172 pairs; mean age 15.56 +/- 5.62 years) enriched for ASD and other neurodevelopmental conditions were examined. Medical history and current physical problems were collected with a validated questionnaire to determine twin’s somatic health. The Social Responsiveness Scale (SRS-2) was used to measure the participant’s severity of autistic traits. Identified somatic health issues with significant within-twin pair differences were tested in relation to both ASD diagnosis and autistic traits in a co-twin control model. Twins with ASD exhibited more neurological and immunological health problems compared to those without ASD (p = 0.005 and p = 0.004, respectively). The intra-pair differences of neurological conditions and SRS-2 score were significantly correlated in monozygotic twins differing for autism traits (r = 0.40, p = 0.001), while the correlation was not found for immunological problems. In addition, a conditional model for analysis of within-twin pair effects revealed an association between neurological problems and clinical ASD diagnosis (Odds ratio per neurological problem 3.15, p = 0.02), as well as autistic traits (beta = 10.44, p = 0.006), after adjusting for possible effects of co-existing attention deficit hyperactivity disorder and general intellectual abilities. Our findings suggest that neurological problems are associated with autism, and that non-shared environmental factors contribute to the overlap for both clinical ASD and autistic traits. Further population-based twin studies are warranted to validate our results and examine in detailed the shared genetic and environmental contributions of neurological problems and ASD.
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7. Sysoeva OV, Smirnov K, Stroganova TA. {{Sensory evoked potentials in patients with Rett syndrome through the lens of animal studies: Systematic review}}. {Clin Neurophysiol};2019 (Nov 21);131(1):213-224.
OBJECTIVE: Systematically review the abnormalities in event related potential (ERP) recorded in Rett Syndrome (RTT) patients and animals in search of translational biomarkers of deficits related to the particular neurophysiological processes of known genetic origin (MECP2 mutations). METHODS: Pubmed, ISI Web of Knowledge and BIORXIV were searched for the relevant articles according to PRISMA standards. RESULTS: ERP components are generally delayed across all sensory modalities both in RTT patients and its animal model, while findings on ERPs amplitude strongly depend on stimulus properties and presentation rate. Studies on RTT animal models uncovered the abnormalities in the excitatory and inhibitory transmission as critical mechanisms underlying the ERPs changes, but showed that even similar ERP alterations in auditory and visual domains have a diverse neural basis. A range of novel approaches has been developed in animal studies bringing along the meaningful neurophysiological interpretation of ERP measures in RTT patients. CONCLUSIONS: While there is a clear evidence for sensory ERPs abnormalities in RTT, to further advance the field there is a need in a large-scale ERP studies with the functionally-relevant experimental paradigms. SIGNIFICANCE: The review provides insights into domain-specific neural basis of the ERP abnormalities and promotes clinical application of the ERP measures as the non-invasive functional biomarkers of RTT pathophysiology.
