scholarly journals Neuroligin-3: A Circuit-Specific Synapse Organizer That Shapes Normal Function and Autism Spectrum Disorder-Associated Dysfunction

2021 ◽  
Vol 14 ◽  
Author(s):  
Motokazu Uchigashima ◽  
Amy Cheung ◽  
Kensuke Futai
Keyword(s):  
Autism Spectrum Disorder ◽  
Molecular Mechanism ◽  
Strong Association ◽  
Critical Role ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Synaptic Signaling ◽  
Syndromic Asd ◽  
Chemical Synapses ◽  
And Function

Chemical synapses provide a vital foundation for neuron-neuron communication and overall brain function. By tethering closely apposed molecular machinery for presynaptic neurotransmitter release and postsynaptic signal transduction, circuit- and context- specific synaptic properties can drive neuronal computations for animal behavior. Trans-synaptic signaling via synaptic cell adhesion molecules (CAMs) serves as a promising mechanism to generate the molecular diversity of chemical synapses. Neuroligins (Nlgns) were discovered as postsynaptic CAMs that can bind to presynaptic CAMs like Neurexins (Nrxns) at the synaptic cleft. Among the four (Nlgn1-4) or five (Nlgn1-3, Nlgn4X, and Nlgn4Y) isoforms in rodents or humans, respectively, Nlgn3 has a heterogeneous expression and function at particular subsets of chemical synapses and strong association with non-syndromic autism spectrum disorder (ASD). Several lines of evidence have suggested that the unique expression and function of Nlgn3 protein underlie circuit-specific dysfunction characteristic of non-syndromic ASD caused by the disruption of Nlgn3 gene. Furthermore, recent studies have uncovered the molecular mechanism underlying input cell-dependent expression of Nlgn3 protein at hippocampal inhibitory synapses, in which trans-synaptic signaling of specific alternatively spliced isoforms of Nlgn3 and Nrxn plays a critical role. In this review article, we overview the molecular, anatomical, and physiological knowledge about Nlgn3, focusing on the circuit-specific function of mammalian Nlgn3 and its underlying molecular mechanism. This will provide not only new insight into specific Nlgn3-mediated trans-synaptic interactions as molecular codes for synapse specification but also a better understanding of the pathophysiological basis for non-syndromic ASD associated with functional impairment in Nlgn3 gene.

Development of Neural Structure and Function in Autism Spectrum Disorder: Potential Implications for Learning Language

2020 ◽  
Vol 29 (4) ◽  
pp. 1783-1797
Author(s):  
Kelly L. Coburn ◽  
Diane L. Williams
Keyword(s):  
Autism Spectrum Disorder ◽  
Language Development ◽  
Diffusion Tensor ◽  
Autism Spectrum ◽  
Language Intervention ◽  
Spectrum Disorder ◽  
Autistic Children ◽  
Neural Structure ◽  
Complex Information ◽  
And Function

Purpose Neurodevelopmental processes that begin during gestation and continue throughout childhood typically support language development. Understanding these processes can help us to understand the disruptions to language that occur in neurodevelopmental conditions, such as autism spectrum disorder (ASD). Method For this tutorial, we conducted a focused literature review on typical postnatal brain development and structural and functional magnetic resonance imaging, diffusion tensor imaging, magnetoencephalography, and electroencephalography studies of the neurodevelopmental differences that occur in ASD. We then integrated this knowledge with the literature on evidence-based speech-language intervention practices for autistic children. Results In ASD, structural differences include altered patterns of cortical growth and myelination. Functional differences occur at all brain levels, from lateralization of cortical functions to the rhythmic activations of single neurons. Neuronal oscillations, in particular, could help explain disrupted language development by elucidating the timing differences that contribute to altered functional connectivity, complex information processing, and speech parsing. Findings related to implicit statistical learning, explicit task learning, multisensory integration, and reinforcement in ASD are also discussed. Conclusions Consideration of the neural differences in autistic children provides additional scientific support for current recommended language intervention practices. Recommendations consistent with these neurological findings include the use of short, simple utterances; repetition of syntactic structures using varied vocabulary; pause time; visual supports; and individualized sensory modifications.

scholarly journals Neurodivergent Themed Neighbourhoods as A Strategy to Enhance the Liveability of Cities: The Blueprint of an Autism Village, Its Benefits to Neurotypical Environments

Urban Science ◽  
2018 ◽  
Vol 2 (2) ◽  
pp. 42 ◽  
Author(s):  
Eurydice Chan
Keyword(s):  
Autism Spectrum Disorder ◽  
Built Environment ◽  
Well Being ◽  
Autism Spectrum ◽  
Design Guidelines ◽  
Spectrum Disorder ◽  
Different Populations ◽  
Limited Option ◽  
Living Environments ◽  
And Function

In the next decades, it is expected that there will be a significant number of adults living with Autism Spectrum Disorder (ASD) who will continue to strive in the neurotypical environment. Despite the recent rise of developments that deviate from the institutional type of facility, many parents continue to voice their struggle to find safe and appropriate living environments for their adult children. The problem is not just the limited option on where to live, financing a home is also another dilemma. Thus, the challenge to provide appropriate living environments coincide with the need to provide meaningful opportunities that allows them to thrive and function in the society. This paper explores the existing design guidelines through recommendations on how spaces can be articulated by considering the value of savant skills and productive vocational skills for individuals living with ASD. This optimistic approach hopes to enlighten built environment practitioners in designing spaces where different populations can co–exist, particularly those with varied abilities. The environmental needs of ASDs and the proposed spatial interventions also extend its benefits to the well–being of neurotypicals. In addition, the participation of the ASD population in the built environment bridges accessibility and spatial experience. Therefore, designing neurodivergent neighbourhoods can be employed as a strategy to improve and enhance the liveability of urban regions.

scholarly journals Autism and Williams syndrome: Dissimilar socio-cognitive profiles with similar patterns of abnormal gene expression in the blood

Autism ◽  
2020 ◽  
pp. 136236132096507
Author(s):  
Amy Niego ◽  
Antonio Benítez-Burraco
Keyword(s):  
Autism Spectrum Disorder ◽  
Autism Spectrum Disorders ◽  
Williams Syndrome ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Cognitive Domain ◽  
Cognitive Profiles ◽  
The Social ◽  
Spectrum Disorders ◽  
And Function

Autism spectrum disorders and Williams syndrome exhibit quite opposite features in the social domain, but also share some common underlying behavioral and cognitive deficits. It is not clear, however, which genes account for the attested differences (and similarities) in the socio-cognitive domain. In this article, we adopted a comparative molecular approach and looked for genes that might be differentially (or similarly) regulated in the blood of subjects with these two conditions. We found a significant overlap between differentially expressed genes compared to neurotypical controls, with most of them exhibiting a similar trend in both conditions, but with genes being more dysregulated in Williams syndrome than in autism spectrum disorders. These genes are involved in aspects of brain development and function (particularly dendritogenesis) and are expressed in brain areas (particularly the cerebellum, the thalamus, and the striatum) of relevance for the autism spectrum disorder and the Williams syndrome etiopathogenesis. Lay abstract Autism spectrum disorders and Williams syndrome are complex cognitive conditions exhibiting quite opposite features in the social domain: whereas people with autism spectrum disorders are mostly hyposocial, subjects with Williams syndrome are usually reported as hypersocial. At the same time, autism spectrum disorders and Williams syndrome share some common underlying behavioral and cognitive deficits. It is not clear, however, which genes account for the attested differences (and similarities) in the socio-cognitive domain. In this article, we adopted a comparative molecular approach and looked for genes that might be differentially (or similarly) regulated in the blood of people with these conditions. We found a significant overlap between genes dysregulated in the blood of patients compared to neurotypical controls, with most of them being upregulated or, in some cases, downregulated. Still, genes with similar expression trends can exhibit quantitative differences between conditions, with most of them being more dysregulated in Williams syndrome than in autism spectrum disorders. Differentially expressed genes are involved in aspects of brain development and function (particularly dendritogenesis) and are expressed in brain areas (particularly the cerebellum, the thalamus, and the striatum) of relevance for the autism spectrum disorder and the Williams syndrome etiopathogenesis. Overall, these genes emerge as promising candidates for the similarities and differences between the autism spectrum disorder and the Williams syndrome socio-cognitive profiles.

scholarly journals Update on Atypicalities of Central Nervous System in Autism Spectrum Disorder

2020 ◽  
Vol 10 (5) ◽  
pp. 309
Author(s):  
Ahmad Naqib Shuid ◽  
Putri Ayu Jayusman ◽  
Nazrun Shuid ◽  
Juriza Ismail ◽  
Norazlin Kamal Nor ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Central Nervous System ◽  
Nervous System ◽  
Signaling Pathway ◽  
Immune Dysregulation ◽  
Autism Spectrum ◽  
Mtor Signaling ◽  
Spectrum Disorder ◽  
Mtor Signaling Pathway ◽  
And Function

Autism spectrum disorder (ASD) is a heterogeneous, behaviorally defined, neurodevelopmental disorder that has been modeled as a brain-based disease. The behavioral and cognitive features of ASD are associated with pervasive atypicalities in the central nervous system (CNS). To date, the exact mechanisms underlying the pathophysiology of ASD still remain unknown and there is currently no cure or effective treatment for this disorder. Many publications implicated the association of ASD with inflammation, immune dysregulation, neurotransmission dysfunction, mitochondrial impairment and cell signaling dysregulation. This review attempts to highlight evidence of the major pathophysiology of ASD including abnormalities in the brain structure and function, neuroglial activation and neuroinflammation, glutamatergic neurotransmission, mitochondrial dysfunction and mechanistic target of rapamycin (mTOR) signaling pathway dysregulation. Molecular and cellular factors that contributed to the pathogenesis of ASD and how they may affect the development and function of CNS are compiled in this review. However, findings of published studies have been complicated by the fact that autism is a very heterogeneous disorder; hence, we addressed the limitations that led to discrepancies in the reported findings. This review emphasizes the need for future studies to control study variables such as sample size, gender, age range and intelligence quotient (IQ), all of which that could affect the study measurements. Neuroinflammation or immune dysregulation, microglial activation, genetically linked neurotransmission, mitochondrial dysfunctions and mTOR signaling pathway could be the primary targets for treating and preventing ASD. Further research is required to better understand the molecular causes and how they may contribute to the pathophysiology of ASD.

Colombian parents of children with autism spectrum disorder: Perceptions, experiences, and expectations

2021 ◽  
Author(s):  
Marie Tejero Hughes ◽  
Sandra Magaña ◽  
Wendy Gonzales ◽  
Giselle Núñez ◽  
Marisol Moreno-Angarita
Keyword(s):  
Autism Spectrum Disorder ◽  
Parent Education ◽  
Critical Role ◽  
Children With Autism ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Future Aspirations ◽  
Services And Supports ◽  
Parent Education Programs ◽  
The Impact

Abstract Families play a critical role in supporting their children with autism spectrum disorder (ASD) and in advocating for their health and educational needs. However, many families around the world experience social, emotional, and financial difficulties, as well as challenges navigating various systems in search for the services and supports their children require. Colombia has made some recent strides in supporting the needs of families of children with ASD, but there is still concern among families that their children are not receiving adequate services. Thus, we were interested in learning more about what it was like to parent a child with ASD in Colombia. In particular, we focused on investigating the families' perceptions, experiences, and aspirations for their child with ASD by conducting focus group interviews. Four primary themes emerged from these interviews with Colombian parents, which included the impact of the disability diagnosis on the family, the systemic and societal challenges they faced, the strengths they saw in their child, and their future aspirations and expectations for their child. Implications for developing culturally responsive parent education programs are discussed.

scholarly journals Downregulation of an Evolutionary Young miR-1290 in an iPSC-Derived Neural Stem Cell Model of Autism Spectrum Disorder

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Dalia Moore ◽  
Brittney M. Meays ◽  
Lepakshe S. V. Madduri ◽  
Farah Shahjin ◽  
Subhash Chand ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Stem Cell ◽  
Neuronal Differentiation ◽  
Neural Stem Cell ◽  
Cell Model ◽  
Critical Role ◽  
Induced Pluripotent Stem Cell ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Induced Pluripotent

The identification of several evolutionary young miRNAs, which arose in primates, raised several possibilities for the role of such miRNAs in human-specific disease processes. We previously have identified an evolutionary young miRNA, miR-1290, to be essential in neural stem cell proliferation and neuronal differentiation. Here, we show that miR-1290 is significantly downregulated during neuronal differentiation in reprogrammed induced pluripotent stem cell- (iPSC-) derived neurons obtained from idiopathic autism spectrum disorder (ASD) patients. Further, we identified that miR-1290 is actively released into extracellular vesicles. Supplementing ASD patient-derived neural stem cells (NSCs) with conditioned media from differentiated control-NSCs spiked with “artificial EVs” containing synthetic miR-1290 oligonucleotides significantly rescued differentiation deficits in ASD cell lines. Based on our earlier published study and the observations from the data presented here, we conclude that miR-1290 regulation could play a critical role during neuronal differentiation in early brain development.

Topography and Function of Challenging Behaviors in Individuals with Autism Spectrum Disorder

2018 ◽  
Vol 2 (2) ◽  
pp. 206-215 ◽  
Author(s):  
Esther Hong ◽  
Dennis R. Dixon ◽  
Elizabeth Stevens ◽  
Claire O. Burns ◽  
Erik Linstead
Keyword(s):  
Autism Spectrum Disorder ◽  
Challenging Behaviors ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
And Function

scholarly journals Prevalence and Phenotypic Impact of Rare Likely Pathogenic Variants in Autism Spectrum Disorder

2020 ◽  
Author(s):  
Behrang Mahjani ◽  
Silvia De Rubeis ◽  
Christina Gustavsson Mahjani ◽  
Maureen Mulhern ◽  
Xinyi Xu ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
De Novo ◽  
Strong Association ◽  
Population Sample ◽  
Population Level ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Single Nucleotide Variants ◽  
Pathogenic Variants ◽  
Pathogenic Cnvs

Abstract Background: Copy number variants (CNVs) and single nucleotide variants (SNVs) are sources of risk for autism spectrum disorder (ASD). The distribution of such pathogenic variants in individuals with ASD and the characterization of those who carry such variants versus those who do not are understudied at the population level. We describe a population sample from Sweden, evaluating the distribution of likely pathogenic variants and their impact on medical, neurological, and psychiatric phenotypes.Methods: The genotyped sample consisted of 1,236 children born in Sweden with autistic disorder, a severe form of ASD (International Classification of Diseases, Tenth Revision, code F84.0.) Of these individuals, CNVs were called from 997, while SNVs were called from 808. Results: Out of 997 individuals from whom CNVs were called, 104 (10.4 %) carried one or more likely pathogenic CNV, including 15q11q13 (n=8), 15q13.3 (n=5), 16p13.11 (n=5), 16p11.11 (n=5), 22q11.2 (n=5). Of 808 individuals assessed by whole-exome sequencing, 69 (8.5%) had a likely pathogenic SNV, including in GRIN2B (n = 6), POGZ (n = 5), SATB1 (n=4), DYNC1H1 (n=4), and CREBBP (n=3). Fourteen individuals carried two likely pathogenic CNVs, and 5 carried a likely pathogenic CNV and SNV. Carriers of likely pathogenic CNVs or SNVs were more likely to have intellectual disability (ID), scholastic skill disorders, and epilepsy, with odds ratios of 2.31 (95%CI, 1.55,3.47), 1.98 (95%CI, 1.19,3.21), and 1.63 (95%CI, 1.08,2.44) respectively. Carriers of likely pathogenic CNVs also showed significant increased rates of congenital anomalies. We compared rates of likely pathogenic CNVs, SNVs, and phenotypes from genotyped AD subjects with and without ID: rates were not significantly different between groups. Limitations: As a case-control cohort, we did not have de novo information to aid in classification. More broadly, there were judgment calls involved in identifying likely pathogenic variants. For these reasons, some misclassification is possible. In addition, phenotypes are defined from medical registers, which may lead to underestimates of milder findings.Conclusions: People with ASD who carry likely pathogenic CNVs or SNVs show increased rates of various comorbidities, most prominently ID. Despite the strong association with ID, conditioning on its presence explains little of the variation for other comorbidities and physical traits.

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