1. Balakrishnan S, Mironov SL. {{Regenerative glutamate release in the hippocampus of Rett syndrome model mice}}. {PloS one}. 2018; 13(9): e0202802.
Excess glutamate during intense neuronal activity is not instantly cleared and may accumulate in the extracellular space. This has various long-term consequences such as ectopic signaling, modulation of synaptic efficacy and excitotoxicity; the latter implicated in various neurodevelopmental and neurodegenerative diseases. In this study, the quantitative imaging of glutamate homeostasis of hippocampal slices from methyl-CpG binding protein 2 knock-out (Mecp2-/y) mice, a model of Rett syndrome (RTT), revealed unusual repetitive glutamate transients. They appeared in phase with bursts of action potentials in the CA1 neurons. Both glutamate transients and bursting activity were suppressed by the blockade of sodium, AMPA and voltage-gated calcium channels (T- and R-type), and enhanced after the inhibition of HCN channels. HCN and calcium channels in RTT and wild-type (WT) CA1 neurons displayed different voltage-dependencies and kinetics. Both channels modulated postsynaptic integration and modified the pattern of glutamate spikes in the RTT hippocampus. Spontaneous glutamate transients were much less abundant in the WT preparations, and, when observed, had smaller amplitude and frequency. The basal ambient glutamate levels in RTT were higher and transient glutamate increases (spontaneous and evoked by stimulation of Schaffer collaterals) decayed slower. Both features indicate less efficient glutamate uptake in RTT. To explain the generation of repetitive glutamate spikes, we designed a novel model of glutamate-induced glutamate release. The simulations correctly predicted the patterns of spontaneous glutamate spikes observed under different experimental conditions. We propose that pervasive spontaneous glutamate release is a hallmark of Mecp2-/y hippocampus, stemming from and modulating the hyperexcitability of neurons.
Lien vers le texte intégral (Open Access ou abonnement)
2. Boland KM, Stichter JP, Beversdorf DQ, Christ SE. {{Brief Report: Flanker Visual Filtering Ability in Older Adolescents with Autism Spectrum Disorder}}. {Journal of autism and developmental disorders}. 2018.
Recent research has documented impaired ability to resist interference from visual distractors in individuals with autism spectrum disorder (ASD) and suggests that this phenomenon may be more pronounced in young versus older children (Christ et al., Neuropsychology 25(6):690-701, 2011). The present study extends previous findings by examining visual filtering inhibitory ability within an older adolescent population. A flanker visual filtering task was administered to 36 adolescents with ASD and 44 adolescents without ASD (age: 11-20 years). Analysis revealed no evidence of group differences in visual filtering performance. Taken together with previous research, these results suggest that during early adolescence the previously observed impairment may resolve or compensatory strategies develop, allowing individuals with ASD to perform as well as their neurotypical peers.
Lien vers le texte intégral (Open Access ou abonnement)
3. Collette D, Brix A, Brennan P, DeRoma N, Muir BC. {{Proloquo2Go Enhances Classroom Performance in Children With Autism Spectrum Disorder}}. {OTJR : occupation, participation and health}. 2018: 1539449218799451.
Independent participation in academic settings is decreased for children who have limited speech and are diagnosed with autism spectrum disorder (ASD). The use of technology with children with ASD changes behavior, assists with making choices, and increases communication; however, no studies evaluated its impact on performance or required support in classroom activities. The objective of this study was to determine whether an iPad with Proloquo2Go would increase independent activity/task performance and reduce required support for children with ASD, during classroom activities compared with no and other forms of technology (i.e., picture exchange communication system [PECS], SMARTBoard). The study compared the use of Proloquo2Go on the iPad to alternative technologies for performance in classroom activities in four children diagnosed with ASD. Using Proloquo2Go to respond to academic opportunities, children required less support than when using no technology, and equal support to when using a PECS or SMARTBoard. Proloquo2Go on the iPad can enhance academic occupational performance in adding voice output and a variety of response choices.
Lien vers le texte intégral (Open Access ou abonnement)
4. Harwood C, Kaczmarek E, Drake D. {{Parental Perceptions of the Nature of the Relationship Children with Autism Spectrum Disorders Share with Their Canine Companion}}. {Journal of autism and developmental disorders}. 2018.
This study examined the role of companion canines in the lives of children with autism spectrum disorder (ASD). Interviews were conducted with 11 mothers of children with ASD (aged 5-12) who owned a canine companion in a multiple case study methodology. Transcript analysis revealed the emergence of five major themes, namely; love and companionship, perception of ownership, comfort and calming influence, canine’s ability to assist the child with understanding their world, and challenging experiences. The social and emotional benefits of companion canine ownership were observed in the majority of cases, particularly when the canine was the preferred companion animal and possessed an appropriate temperament suitable to cohabit with children who possess unique social and sensory needs.
Lien vers le texte intégral (Open Access ou abonnement)
5. Jiao X, Yu D, Cao T, Huang F. {{Serum miRNA expression profiling reveals miR-486-3p may play a significant role in the development of autism by targeting ARID1B}}. {Neuroreport}. 2018.
Recent studies have implicated microRNAs (miRNAs) in autism and have supported changes in serum miRNA expression profile. We proposed to analyze miRNA expression and its target genes related to regulatory networks in autism within a cohort of Chinese patients. The aim of this study was to explore the dysregulation of miRNAs in autism and investigate the potential mechanistic implications in the pathogenesis of autism. MiRNA was isolated from the serum samples of 20 patients with autism and 23 controls. Dysfunctional miRNAs were identified using miRNA microarray analyses. We used quantitative reverse transcription-PCR to examine the four differentially expressed miRNAs. The target gene of miR-486-3p was confirmed by luciferase assay and miRNA transfection in SH-SY5Y cell lines. A total of 77 differentially expressed miRNAs were found in the miRNA microarray analysis of two patients with autism compared with three controls. On the basis of the microarray results, quantitative reverse transcription-PCR analysis indicated that miR-557 and miR-486-3p expression levels were significantly increased (P<0.05) in 18 patients with autism compared with 20 controls. Overexpression of miR-486-3p decreased ARID1B mRNA and protein levels (P<0.05), whereas inhibition of miR-486-3p increased the mRNA and protein levels of ARID1B in SH-SY5Y cell lines. Luciferase activity was significantly decreased compared with the control group (P<0.05) after cells were co-transfected with miR-486-3p mimics and ARID1B 3'-untranslated region. Our study has highlighted that miR-486-3p expression is increased in serum of patients with autism and supports that miR-486-3p inhibits the expression of ARID1B. Lien vers le texte intégral (Open Access ou abonnement)
6. Velthorst E, Froudist-Walsh S, Stahl E, Ruderfer D, Ivanov I, Buxbaum J. {{Genetic risk for schizophrenia and autism, social impairment and developmental pathways to psychosis}}. {Translational psychiatry}. 2018; 8(1): 204.
While psychotic experiences (PEs) are assumed to represent psychosis liability, general population studies have not been able to establish significant associations between polygenic risk scores (PRS) and PEs. Previous work suggests that PEs may only represent significant risk when accompanied by social impairment. Leveraging data from the large longitudinal IMAGEN cohort, including 2096 14-year old adolescents that were followed-up to age 18, we tested whether the association between polygenic risk and PEs is mediated by (increasing) impairments in social functioning and social cognitive processes. Using structural equation modeling (SEM) for the subset of participants (n = 643) with complete baseline and follow-up data, we examined pathways to PEs. We found that high polygenic risk for schizophrenia (p = 0.014), reduced brain activity to emotional stimuli (p = 0.009) and social impairments in late adolescence (p < 0.001; controlling for functioning in early adolescence) each independently contributed to the severity of PEs at age 18. The pathway between polygenic risk for autism spectrum disorder and PEs was mediated by social impairments in late adolescence (indirect pathway; p = 0.025). These findings point to multiple direct and indirect pathways to PEs, suggesting that different processes are in play, depending on genetic loading, and environment. Our results suggest that treatments targeting prevention of social impairment may be particularly promising for individuals at genetic risk for autism in order to minimize risk for psychosis. Lien vers le texte intégral (Open Access ou abonnement)
7. Yang Q, Huang P, Li C, Fang P, Zhao N, Nan J, Wang B, Gao W, Cui LB. {{Mapping alterations of gray matter volume and white matter integrity in children with autism spectrum disorder: evidence from fMRI findings}}. {Neuroreport}. 2018; 29(14): 1188-92.
This study aimed to identify the neuroanatomical substrates and white matter connectivity in children with autism spectrum disorder (ASD) and the association between gray matter and structural connectivity. A total of 36 children including patients with ASD and healthy controls between 6 and 15 years of age were enrolled in this study. High-resolution structural MRI and functional MRI were performed and analyzed using voxel-based morphometry and tract-based spatial statistics. The relationship between gray matter volume and structural connectivity was generated using Pearson correlation analysis. Voxel-based morphometry analysis showed significantly reduced areas of gray matter in the left cerebellum. Tract-based spatial statistics analysis showed white matter abnormalities in several distinct clusters within the right inferior frontal gyrus (opercular part), the left inferior parietal lobule, and the right mentary motor area. Neither ASD nor healthy controls showed a significant correlation between gray matter volume and white matter integrity. Our study confirmed the presence of several structural and regional abnormalities in ASD children. These findings suggest that there are significant differences in some brain regions in children with autism relative to healthy children, but no association between them.
