1. {{Correction to Supporting Information for Gadad et al., Administration of thimerosal-containing vaccines to infant rhesus macaques does not result in autism-like behavior or neuropathology}}. {Proc Natl Acad Sci U S A};2015 (Dec 8);112(49):E6827.
Lien vers le texte intégral (Open Access ou abonnement)
2. Li J, Chai A, Wang L, Ma Y, Wu Z, Yu H, Mei L, Lu L, Zhang C, Yue W, Xu L, Rao Y, Zhang D. {{Synaptic P-Rex1 signaling regulates hippocampal long-term depression and autism-like social behavior}}. {Proc Natl Acad Sci U S A};2015 (Dec 15);112(50):E6964-E6972.
Autism spectrum disorders (ASDs) are a group of highly inheritable mental disorders associated with synaptic dysfunction, but the underlying cellular and molecular mechanisms remain to be clarified. Here we report that autism in Chinese Han population is associated with genetic variations and copy number deletion of P-Rex1 (phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 1). Genetic deletion or knockdown of P-Rex1 in the CA1 region of the hippocampus in mice resulted in autism-like social behavior that was specifically linked to the defect of long-term depression (LTD) in the CA1 region through alteration of AMPA receptor endocytosis mediated by the postsynaptic PP1alpha (protein phosphase 1alpha)-P-Rex1-Rac1 (Ras-related C3 botulinum toxin substrate 1) signaling pathway. Rescue of the LTD in the CA1 region markedly alleviated autism-like social behavior. Together, our findings suggest a vital role of P-Rex1 signaling in CA1 LTD that is critical for social behavior and cognitive function and offer new insight into the etiology of ASDs.
Lien vers le texte intégral (Open Access ou abonnement)
3. Memarian A, Mehrpisheh S. {{Therapeutic and Ethical Dilemma of Puberty and Menstruation Problems in an Intellectually Disabled (Autistic) Female: a Case Report}}. {Acta Med Iran};2015 (Oct);53(10):663-666.
Intellectual disability is a term used when a person has certain limitations in mental functioning and skills. Autism is a group of developmental brain disorders, collectively called autism spectrum disorder (ASD). Teenagers with learning and physical disabilities are more likely to have menstrual problems compared to the general populations. The parents of a 12-year-old girl with autism spectrum disorder and intellectual disability referred to the coroner due to her numerous problems of puberty (menstruation) including: poor hygiene and polluting herself and the environment, not allowing to put or change the pads and changes in mood and physical health prior period, requested for the surgery (hysterectomy). In legal medicine organization after reviewing the medical records, physical exams and medical consultations with a gynecologist and psychiatric, surgery was not accepted. Hysterectomy (surgery) due to the age of the child, either physically or morally is not recommended. The use of hormone replacement therapy has side effects such as osteoporosis. In these cases, it seems noninvasive methods (behavioral therapy and learning care skills) under the welfare experts is also more effective and morally.
4. O’Reilly M, Lester JN, Muskett T. {{Discourse/Conversation Analysis and Autism Spectrum Disorder}}. {J Autism Dev Disord};2015 (Nov 28)
Lien vers le texte intégral (Open Access ou abonnement)
5. Sacco R, Gabriele S, Persico AM. {{Head circumference and brain size in autism spectrum disorder: A systematic review and meta-analysis}}. {Psychiatry Res};2015 (Nov 30);234(2):239-251.
Macrocephaly and brain overgrowth have been associated with autism spectrum disorder. We performed a systematic review and meta-analysis to provide an overall estimate of effect size and statistical significance for both head circumference and total brain volume in autism. Our literature search strategy identified 261 and 391 records, respectively; 27 studies defining percentages of macrocephalic patients and 44 structural brain imaging studies providing total brain volumes for patients and controls were included in our meta-analyses. Head circumference was significantly larger in autistic compared to control individuals, with 822/5225 (15.7%) autistic individuals displaying macrocephaly. Structural brain imaging studies measuring brain volume estimated effect size. The effect size is higher in low functioning autistics compared to high functioning and ASD individuals. Brain overgrowth was recorded in 142/1558 (9.1%) autistic patients. Finally, we found a significant interaction between age and total brain volume, resulting in larger head circumference and brain size during early childhood. Our results provide conclusive effect sizes and prevalence rates for macrocephaly and brain overgrowth in autism, confirm the variation of abnormal brain growth with age, and support the inclusion of this endophenotype in multi-biomarker diagnostic panels for clinical use.
Lien vers le texte intégral (Open Access ou abonnement)
6. Ulbrich L, Favaloro FL, Trobiani L, Marchetti V, Patel V, Pascucci T, Comoletti D, Marciniak SJ, De Jaco A. {{Autism associated R451C mutation in Neuroligin3 leads to the activation of the unfolded protein response in a PC12 Tet-On inducible system}}. {Biochem J};2015 (Nov 30)
Several forms of monogenic heritable autism spectrum disorders are associated to mutations in the neuroligin genes. The autism-linked substitution arginine 451 to cysteine (R451C) in neuroligin3induces local misfolding of its extracellular domain, causing partial retention in the endoplasmic reticulum (ER) of expressing cells. We have generated a PC12 Tet-On cell model system with inducible expression of wild type or R451C neuroligin3 to investigate if there is activation of the unfolded protein response (UPR) as a result of misfolded protein retention. As a positive control for protein misfolding, we also expressed the severely disrupted mutant G221R neuroligin3, which is known to be completely retained within the ER. Our data show that overexpression of either R451C or G221R mutant proteins leads to the activation of all three signaling branches of the UPR downstream of the stress sensors ATF6, IRE1 and PERK. Each branch displayed different activation profiles that partially correlated with the degree of misfolding caused by each mutation. We also show that upregulation of BiP and CHOP was induced by both mutant proteins but not by wild type neuroligin3, both in proliferative cells and cells differentiated to a neuronal-like phenotype. Collectively, our data show that mutant R451C neuroligin3 activates the UPR in a novel cell model system, suggesting that this cellular response may have a role in monogenic forms of autism characterized by misfolding mutations.
Lien vers le texte intégral (Open Access ou abonnement)
7. Veatch OJ, Reynolds A, Katz T, Weiss SK, Loh A, Wang L, Malow BA. {{Sleep in Children With Autism Spectrum Disorders: How Are Measures of Parent Report and Actigraphy Related and Affected by Sleep Education?}}. {Behav Sleep Med};2015 (Nov 30):1-12.
Sleep disturbance is common in children with autism, resulting in a great need for effective treatments. To evaluate treatments for sleep disturbance in this population, it is critical to understand the relationship between measures of sleep captured by parent report and objective measures. The Children’s Sleep Habits Questionnaire (CSHQ) and actigraphy-measured data from 80 children with autism and sleep-onset delay were evaluated. Reported problems with sleep-onset delay were concurrent with sleep duration problems in 66% of children, night wakings in 72% of children, and bedtime resistance in 66% of children; 38% of children were reported to have problems with all CSHQ insomnia domains. Actigraphy-measured sleep duration was correlated with estimates using CSHQ-reported bed and wake times.
