Pubmed du 15/09/18

samedi 15 septembre 2018

1. Ahmad SF, Ansari MA, Nadeem A, Bakheet SA, Alshammari MA, Khan MR, Alsaad AMS, Attia SM. S3I-201, a selective Stat3 inhibitor, restores neuroimmune function through upregulation of Treg signaling in autistic BTBR T(+) Itpr3(tf)/J mice. Cell Signal ;2018 (Sep 10) ;52:127-136.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder whose symptoms include communication deficits, a lack of social skills, and stereotyped repetitive behaviors. We used BTBR T(+) Itpr3(tf)/J (BTBR) mice, a model that demonstrates most of the core behavioral features of ASD, such as decreased sociability and high levels of repetitive behaviors. Currently, there is no treatment available that is able to improve most of the ASD disorder symptoms ; thus, finding novel therapies is immediately required. Stat3 inhibitors are potential targets in the treatment of several immune disorders. The aim of the present study was to investigate the effects of S3I-201, a selective Stat3 inhibitor, to determine its potential mechanism in BTBR mice. In this study, we first examined the effects of S3I-201 on repetitive behavior and marble burying. We also examined the treatment of S3I-201 on Th1 (IFN-gamma and T-bet), Th17 (IL-17A, RORgammat, Stat3, IL-21, and IL-22), and T regulatory (Treg, Foxp3 and Helios) production in spleen CD4(+) T cells. We further assessed Th1, Th17, and Treg mRNA and protein expression levels in brain tissues. S3I-201 treatment in BTBR mice significantly prevents marble burying and repetitive behavior. Furthermore, S3I-201 administration causes a considerable decrease in IFN-gamma, T-bet, IL-17A, RORgammat, Stat3, IL-21, and IL-22 levels, and increases in Foxp3 and Helios production CD4(+) T cells in BTBR mice. Additionally, S3I-201 treatment also significantly decreases Th1 and Th17 levels, and increases Treg mRNA and protein expression levels. Therefore, these results suggest that S3I-201 could be considered as a therapeutic option for ASD.

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2. Campisi L, Imran N, Nazeer A, Skokauskas N, Azeem MW. Autism spectrum disorder. Br Med Bull ;2018 (Sep 1) ;127(1):91-100.

Sources of data : This article is based on key recent published literature including international guidelines and relevant reviews and meta-analyses. Authors have also supplemented this material with their own clinical experience. Areas of agreement : There is an agreement that autism spectrum disorder (ASD) have a strong hereditary component. There is also a consensus that the reported prevalence estimates have increased in the last 5 years. There is strong support for using the broader spectrum disorder conceptualization of the DSM-5. Areas of controversy : Higher public awareness of ASD has generated several controversial theories of causation. We review a number of environmental risk factors receiving media attention including : vaccines, mercury, heavy metal exposure and Selective Serotonin Uptake Inhibitors (SSRIs). Popular yet controversial treatment interventions are discussed. Early diagnostic screening tools are also addressed. Growing points : There is increasing scientific interest in identifying biomarkers of autism with potential for early diagnosis, prognostic indicators and predictive treatment responses. We review evidence from genetics, neuroimaging and eye tracking as candidate biomarkers. Area timely for developing research : Family studies point to a strong hereditary component in the aetiology of autism. However these studies have not established 100% concordance rates, suggesting a role for environmental factors. The gene-environment interplay has not received enough attention in scientific research. This represents an important new avenue for research in ASD.

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3. Cappuccio G, Bernardo P, Raiano E, Pinelli M, Alagia M, Esposito M, Della Casa R, Strisciuglio P, Brunetti-Pierri N, Bravaccio C. Pain and sleep issues in Rett syndrome and other neurodevelopmental disorders. Acta Paediatr ;2018 (Sep 14)

Rett syndrome is a severe neurodevelopmental disorder, mostly caused by a MECP2 gene mutation, with some overlaps with autism spectrum disorders and cerebral palsy. Pain perception is potentially abnormal in children with neurodevelopmental disorders and higher levels of pain and discomfort are expected in Rett syndrome, due to issues such as scoliosis, constipation, gastrointestinal problems and self-injuries. Despite this, atypical pain expressions have been reported in Rett syndrome patients that give the impression that they are not in pain (1). Impaired nociception has been directly linked to the MECP2 gene, which contributes to the modulate genes involved in nociceptive circuitry (1). Pain issues are also general concerns among children with disabilities. Reports have suggested that patients with autism spectrum are hyposensitive to different pain stimuli. This article is protected by copyright. All rights reserved.

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4. Chin EWM, Lim WM, Ma D, Rosales FJ, Goh ELK. Choline Rescues Behavioural Deficits in a Mouse Model of Rett Syndrome by Modulating Neuronal Plasticity. Mol Neurobiol ;2018 (Sep 15)

Rett syndrome (RTT) is a postnatal neurodevelopmental disorder that primarily affects girls, with 95% of RTT cases resulting from mutations in the methyl-CpG-binding protein 2 (MECP2) gene. Choline, a dietary micronutrient found in most foods, has been shown to be important for brain development and function. However, the exact effects and mechanisms are still unknown. We found that 13 mg/day (1.7 x required daily intake) of postnatal choline treatment to Mecp2-conditional knockout mice rescued not only deficits in motor coordination, but also their anxiety-like behaviour and reduced social preference. Cortical neurons in the brains of Mecp2-conditional knockout mice supplemented with choline showed enhanced neuronal morphology and increased density of dendritic spines. Modelling RTT in vitro by knocking down the expression of the MeCP2 protein with shRNA, we found that choline supplementation to MeCP2-knockdown neurons increased their soma sizes and the complexity of their dendritic arbors. Rescue of the morphological defects could lead to enhanced neurotransmission, as suggested by an observed trend of increased expression of synaptic proteins and restored miniature excitatory postsynaptic current frequency in choline-supplemented MeCP2-knockdown neurons. Through the use of specific inhibitors targeting each of the known physiological pathways of choline, synthesis of phosphatidylcholine from choline was found to be essential in bringing about the changes seen in the choline-supplemented MeCP2-knockdown neurons. Taken together, these data reveal a role of choline in modulating neuronal plasticity, possibly leading to behavioural changes, and hence, a potential for using choline to treat RTT.

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5. Coderre EL, Cohn N, Slipher SK, Chernenok M, Ledoux K, Gordon B. Visual and linguistic narrative comprehension in autism spectrum disorders : Neural evidence for modality-independent impairments. Brain Lang ;2018 (Sep 11) ;186:44-59.

Individuals with autism spectrum disorders (ASD) have notable language difficulties, including with understanding narratives. However, most narrative comprehension studies have used written or spoken narratives, making it unclear whether narrative difficulties stem from language impairments or more global impairments in the kinds of general cognitive processes (such as understanding meaning and structural sequencing) that are involved in narrative comprehension. Using event-related potentials (ERPs), we directly compared semantic comprehension of linguistic narratives (short sentences) and visual narratives (comic panels) in adults with ASD and typically-developing (TD) adults. Compared to the TD group, the ASD group showed reduced N400 effects for both linguistic and visual narratives, suggesting comprehension impairments for both types of narratives and thereby implicating a more domain-general impairment. Based on these results, we propose that individuals with ASD use a more bottom-up style of processing during narrative comprehension.

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6. Ghaderi G, Watson SL. "In Medical School, You Get Far More Training on Medical Stuff than Developmental Stuff" : Perspectives on ASD from Ontario Physicians. J Autism Dev Disord ;2018 (Sep 15)

This study investigated the knowledge and perceived competence of Ontario physicians regarding the diagnosis and treatment of ASDs. Previous research demonstrates that many physicians would like more education regarding diagnosis and treatment of autism spectrum disorders (ASDs). Twenty-seven Ontario physicians filled out a questionnaire and participated in a semi-structured interview. Findings revealed that despite participants’ high perceived knowledge regarding diagnosis and treatment of ASDs, they feel uncomfortable in providing care for this population. Furthermore, many participants stated diagnosing and treating ASDs is not within their scope of practice. Findings have implications for increasing physicians’ knowledge of diagnosis and treatment of ASDs as well as what is required to enhance healthcare for individuals with ASDs and their families.

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7. Prihodova I, Dudova I, Mohaplova M, Hrdlicka M, Nevsimalova S. Childhood narcolepsy and autism spectrum disorders : four case reports. Sleep Med ;2018 (Aug 9) ;51:167-170.

BACKGROUND : Childhood narcolepsy is associated with various emotional, behavioural and cognitive dysfunctions as well as with psychiatric and neurodevelopmental disorders : anxiety, depression, attention deficit hyperactivity disorder and psychosis. A relationship between these conditions is unclear - comorbidity or similar pathophysiological mechanisms can be suggested. OBJECTIVE : We reported four children with narcolepsy type 1 (NT1) and autism spectrum disorder (ASD) - Asperger syndrome (AS). RESULTS AND CONCLUSION : To the best of our knowledge co-occurrence of NT1 and AS has not been described in the literature as noted in this report.

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8. Ridderinkhof A, de Bruin EI, van den Driesschen S, Bogels SM. Attention in Children With Autism Spectrum Disorder and the Effects of a Mindfulness-Based Program. J Atten Disord ;2018 (Sep 15):1087054718797428.

OBJECTIVE : Children with autism spectrum disorder (ASD) show atypical attention. Mindfulness-based programs (MBPs), with self-regulation of attention as a basic component, could benefit these children. METHOD : We investigated how 49 children with ASD differed from 51 typically developing (TD) children in their attention systems ; and whether their attention systems were improved by an MBP for children and their parents (MYmind), using a cognitive measure of attention, the Attention Network Test. RESULTS : Children with ASD did not differ from TD children in the speed of the attention systems, but were somewhat less accurate in their orienting and executive attention. Also, MYmind did not significantly improve attention, although trend effects indicated improved orienting and executive attention. Robustness checks supported these improvements. CONCLUSION : Trend effects of the MBP on the attention systems of children with ASD were revealed, as well as minor differences between children with ASD and TD children in their attention systems.

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9. Sakaguchi A, Yamashita Y, Ishii T, Uehara T, Kosaki K, Takahashi T, Takenouchi T. Further evidence of a causal association between AGO1, a critical regulator of MicroRNA formation, and intellectual disability/autism spectrum disorder. Eur J Med Genet ;2018 (Sep 10)

Among the many regulators of microRNA formation, Argonaute 1 (AGO1) plays critical roles in RNA interference, which controls a wide range of biological activities. Recent large-scale genomic studies have identified at least five patients with intellectual disability/autism spectrum disorder who had de novo mutations in AGO1, but detailed clinical information was not available. The recognizable clinical features that are associated with AGO1 mutations remain to be determined. The proposita was a 15-year-old girl with diffuse hypotonia, infrequent seizures, and intellectual disability with an intellectual quotient of 41. She had characteristic facial features consisting of telecanthus, wide nasal bridge with bulbous nasal tip, and a round face with downslanted palpebral fissures. Serial computed tomography scans showed progressive calcification in the globus pallidus that became evident during childhood. A whole exome analysis in trio revealed a de novo heterozygous mutation in AGO1, i.e., c.595G>A p.(Gly199Ser). The distinctive facial features, i.e., telecanthus, wide nasal bridge with bulbous nasal tip, and a round face with downslanted palpebral fissures, closely resembled previously reported patients who had a chromosomal microdeletion encompassing AGO1 locus. The combinatory phenotype of such characteristic facial features and radiographic features, i.e. progressive calcification in the caudate, in the presently reported patient suggest that AGO1 mutations lead to a syndromic form of intellectual disability/autism spectrum disorder. Distinctive facial features with early and progressive calcification in the globus pallidus may be suggestive of the presence of AGO1 mutations.

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10. Syriopoulou-Delli CK, Polychronopoulou SA, Kolaitis GA, Antoniou AG. Views of Teachers on Anxiety Symptoms in Students with Autism Spectrum Disorder. J Autism Dev Disord ;2018 (Sep 15)

People with autism spectrum disorder (ASD) exhibit comorbidity with anxiety. The aim of this study was the investigation of the perception of teachers on anxiety in school children with ASD. The Scale Teacher Response (SAS-TR) questionnaire was completed by 291 special education and 118 general education teachers, providing data on students in their classes with ASD and of typical development (TD), respectively. According to the total scores on SAS-TR, 46.8% of the children with ASD presented levels of anxiety within the clinical spectrum compared with 15.3% of the children of TD. Gender and age were not associated with the anxiety scores, but in the children with ASD, higher intelligence quotient (IQ) was weakly, and better verbal skills more strongly correlated with a higher anxiety level. Teachers’ awareness of anxiety symptoms in children with ASD may contribute to their social inclusion.

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11. Tang M, Lu L, Xie F, Chen L. SUMOylation of Fragile X Mental Retardation Protein : A Critical Mechanism of FMRP-Mediated Neuronal Function. Neurosci Bull ;2018 (Sep 15)

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12. Vigli D, Cosentino L, Raggi C, Laviola G, Woolley-Roberts M, De Filippis B. Chronic treatment with the phytocannabinoid Cannabidivarin (CBDV) rescues behavioural alterations and brain atrophy in a mouse model of Rett syndrome. Neuropharmacology ;2018 (Sep 15) ;140:121-129.

Rett syndrome (RTT) is a rare neurodevelopmental disorder, characterized by severe behavioural and physiological symptoms. RTT is caused by mutations in the MECP2 gene in about 95% of cases and to date no cure is available. The endocannabinoid system modulates several physiological processes and behavioural responses that are impaired in RTT and its deregulation has been associated with neuropsychiatric disorders which have symptoms in common with RTT. The present study evaluated the potential therapeutic efficacy for RTT of cannabidivarin (CBDV), a non-psychotropic phytocannabinoid from Cannabis sativa that presents antagonistic properties on the G protein-coupled receptor 55 (GPR55), the most recently identified cannabinoid receptor. Present results demonstrate that systemic treatment with CBDV (2, 20, 100 mg/Kg ip for 14 days) rescues behavioural and brain alterations in MeCP2-308 male mice, a validated RTT model. The CBDV treatment restored the compromised general health status, the sociability and the brain weight in RTT mice. A partial restoration of motor coordination was also observed. Moreover, increased levels of GPR55 were found in RTT mouse hippocampus, suggesting this G protein-coupled receptor as new potential target for the treatment of this disorder. Present findings highlight for the first time for RTT the translational relevance of CBDV, an innovative therapeutic agent that is under active investigation in the clinical setting.

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13. Zucker KJ, VanderLaan DP. Corrections to Oien, Cicchetti, and Nordahl-Hansen’s (2018) "Gender Dysphoria, Sexuality and Autism Spectrum Disorder : A Systematic Map Review". J Autism Dev Disord ;2018 (Sep 15)

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