Imbalance of laminar-specific excitatory and inhibitory circuits of the orbitofrontal cortex in autism
ConclusionsThe balance between excitation and inhibition in OFC is at the core of its function, assessing and integrating emotional and social cues with internal states and external inputs. Our preliminary results provide evidence for laminar-specific changes in the ratio of excitation/inhibition in OFC of adults with ASD, with an overall weakening and likely disorganization of excitatory signals and a relative strengthening of local inhibition. These changes likely underlie pathology of major OFC communications with limbic or other cortices and the amygdala in individuals with ASD, and may provide the anatomic basis for d...
Source: Molecular Autism - October 20, 2020 Category: Molecular Biology Source Type: research
Pharmacological intervention to restore connectivity deficits of neuronal networks derived from ASD patient iPSC with a TSC2 mutation
ConclusionsOur observations suggest that there is a reduction in the network connectivity of the in vitro neuronal network associated with ASD patients withTSC2 mutation, which may arise via an excitatory/inhibitory imbalance due to increased GABA-signalling at inhibitory synapses. This abnormality can be effectively suppressed via activation of ULK1. (Source: Molecular Autism)
Source: Molecular Autism - October 19, 2020 Category: Molecular Biology Source Type: research
Social attention to activities in children and adults with autism spectrum disorder: effects of context and age
ConclusionsDifferences in attention to faces could constitute a feature discriminative between individuals with and without ASD across the lifespan, whereas between-group differences in looking at activities may shift with development. These findings may have applications in the search for underlying biological indicators specific to ASD.Trial registration ClinicalTrials.gov identifier NCT02668991. (Source: Molecular Autism)
Source: Molecular Autism - October 19, 2020 Category: Molecular Biology Source Type: research
White matter alterations in autism spectrum disorder and attention-deficit/hyperactivity disorder in relation to sensory profile
ConclusionsThese results indicate that white matter alteration and their relationships to sensory symptoms are largely shared between ASD and ADHD, with localized abnormalities showing significant between-diagnosis differences within DD. (Source: Molecular Autism)
Source: Molecular Autism - October 19, 2020 Category: Molecular Biology Source Type: research
Ribosome profiling in mouse hippocampus: plasticity-induced regulation and bidirectional control by TSC2 and FMRP
ConclusionThese results suggest a molecular basis for bidirectional regulation of synaptic plasticity and behavior by TSC2 and FMRP. Our study also suggests that altered mGluR-regulated translation elongation contributes to impaired synaptic plasticity inTsc2+/ − mice. (Source: Molecular Autism)
Source: Molecular Autism - October 14, 2020 Category: Molecular Biology Source Type: research
De novo missense variants disrupting protein –protein interactions affect risk for autism through gene co-expression and protein networks in neuronal cell types
ConclusionsDisrupted protein interactions identify gene sets involved in risk for ASD. Their gene expression during brain development and within cell types highlights how they relate to ASD. (Source: Molecular Autism)
Source: Molecular Autism - October 8, 2020 Category: Molecular Biology Source Type: research
Functional relationships between recessive inherited genes and genes with de novo variants in autism spectrum disorder
ConclusionsASD RIGs were functionally associated with DNGs; however, they exhibited higher heterogeneity than DNGs. (Source: Molecular Autism)
Source: Molecular Autism - October 5, 2020 Category: Molecular Biology Source Type: research
Chd8 haploinsufficiency impairs early brain development and protein homeostasis later in life
ConclusionsCollectively, these data suggest that UPR/ER stress pathways are reduced in the cerebral cortex of agedChd8V986*/+ mice. Our study uncovers neurodevelopmental and age-related phenotypes inChd8V986*/+ mice and highlights the importance of controlling for age when studyingChd8 haploinsufficient mice. (Source: Molecular Autism)
Source: Molecular Autism - October 4, 2020 Category: Molecular Biology Source Type: research
Autistic traits, systemising, empathising, and theory of mind in transgender and non-binary adults
ConclusionsThe current findings suggest a “masculinised” autism-related profile and reduced ToM in transgender men and in non-binary AFAB. These findings might be interpreted to support the extreme male brain theory of autism and the mindblindness theory. Further research is needed to corroborate these findings. (Source: Molecular Autism)
Source: Molecular Autism - September 28, 2020 Category: Molecular Biology Source Type: research
Differential mirror neuron system (MNS) activation during action observation with and without social-emotional components in autism: a meta-analysis of neuroimaging studies
ConclusionThe MNS is impaired in ASD. The abnormal activation patterns were found to be modulated by the nature of stimuli and age, which might explain the contradictory results from earlier studies on the “broken mirror neuron” debate. (Source: Molecular Autism)
Source: Molecular Autism - September 28, 2020 Category: Molecular Biology Source Type: research
Enhanced social learning of threat in adults with autism
ConclusionsThe enhanced social threat learning in individuals with ASD may be linked to difficulties using visual attention and mental state attributions to downregulate their emotion. (Source: Molecular Autism)
Source: Molecular Autism - September 21, 2020 Category: Molecular Biology Source Type: research
Assessing the requirements of prenatal UBE3A expression for rescue of behavioral phenotypes in a mouse model for Angelman syndrome
ConclusionsOur findings provide further important insights in the requirement of UBE3A expression during brain development. We found that loss of up to 50% of UBE3A protein during prenatal mouse brain development does not significantly impact the assessed mouse behavioral phenotypes. Together with previous findings, our results indicate that the most critical function for mouse UBE3A lies in the early postnatal period between birth and P21. (Source: Molecular Autism)
Source: Molecular Autism - September 17, 2020 Category: Molecular Biology Source Type: research
Autism spectrum disorder at the crossroad between genes and environment: contributions, convergences, and interactions in ASD developmental pathophysiology
AbstractThe complex pathophysiology of autism spectrum disorder encompasses interactions between genetic and environmental factors. On the one hand, hundreds of genes, converging at the functional level on selective biological domains such as epigenetic regulation and synaptic function, have been identified to be either causative or risk factors of autism. On the other hand, exposure to chemicals that are widespread in the environment, such as endocrine disruptors, has been associated with adverse effects on human health, including neurodevelopmental disorders. Interestingly, experimental results suggest an overlap in the ...
Source: Molecular Autism - September 9, 2020 Category: Molecular Biology Source Type: research
Autism-associated variants of neuroligin 4X impair synaptogenic activity by various molecular mechanisms
ConclusionsThese data suggest that reduced amounts of the functional NL4X protein on the cell surface is a common mechanism by which point mutants of the NL4X protein cause psychiatric disorders, although different molecular mechanisms are thought to be involved. Furthermore, these results highlight that the precision medicine approach based on genetic and cell biological analyses is important for the development of therapeutics for psychiatric disorders. (Source: Molecular Autism)
Source: Molecular Autism - August 31, 2020 Category: Molecular Biology Source Type: research
Dissecting the phenotypic heterogeneity in sensory features in autism spectrum disorder: a factor mixture modelling approach
ConclusionSensory features can be best described by three homogeneous sensory subgroups that differ in sensory severity gradients along seven continuous factor scores. Identified sensory subgroups were further differentiated by the severity of core and co-occurring symptoms, and level of adaptive functioning, providing novel evidence on the associated clinical correlates of sensory subgroups. These sensory subgroups provide a platform to further interrogate the neurobiological and genetic correlates of altered sensory processing in ASD. (Source: Molecular Autism)
Source: Molecular Autism - August 30, 2020 Category: Molecular Biology Source Type: research
