Experimental Models to Study Autism Spectrum Disorders: hiPSCs, Rodents and Zebrafish

Autism Spectrum Disorders (ASD) affect around 1.5% of the global population, which manifest alterations in communication and socialization, as well as repetitive behaviors or restricted interests. ASD is a complex disorder with known environmental and genetic contributors; however, ASD etiology is far from being clear. In the past decades, many efforts have been put into developing new models to study ASD, both in vitro and in vivo. These models have a lot of potential to help to validate some of the previously associated risk factors to the development of the disorder, and to test new potential therapies that help to alleviate ASD symptoms. The present review is focused on the recent advances towards the generation of models for the study of ASD, which would be a useful tool to decipher the bases of the disorder, as well as to conduct drug screenings that hopefully lead to the identification of useful compounds to help patients deal with the symptoms of ASD.

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SOCIAL STATUS AND GUT MICROBIAL DYSBIOSIS IN ADULTS AND CHILDREN WITH AUTISM SPECTRUM DISORDERS: A PROFOUND REVIEW OF THE AVAILABLE LITERATURE SOURCES

Journal of IMAB - Annual Proceeding (Scientific Papers) ◽

10.5272/jimab.2021273.3939 ◽

2021 ◽

Vol 27 (3) ◽

pp. 3939-3946

Author(s):

Sevginar Ibryamova ◽

◽

Veselin Petkov ◽

Tsveteslava Ignatova-Ivanova ◽

Georgi Kolev ◽

...

Keyword(s):

Autism Spectrum Disorders ◽

Behavioral Problems ◽

Autism Spectrum ◽

Repetitive Behaviors ◽

Diagnostic Methods ◽

Restricted Interests ◽

Microbial Dysbiosis ◽

Gastrointestinal Problems ◽

Adults And Children ◽

Spectrum Disorders

Autism is a complex disorder without a specific diagnosis, so the disease is defined by its specific characteristics described in the literature as cognitive defects, social, communication and behavioral problems, repetitive behaviors, unusual sensitivity to stimuli such as noise, restricted interests, and self stimulation. There are many models in the literature explaining the biology of autism, which are based on genetics, immunity, various environmental factors and diet. There is a lot of literature data that people with Autism Spectrum Disorders (ASD) often have gastrointestinal problems that also affect their behavior. ASD suffer developmental disabilities from an early age, which can be both physical and psychological. Often people suffer these problems even throughout their lives. This review aims to provide basic information on definitions, historical data, diagnostic methods, behavioral etiology, gastrointestinal and social problems in adults and children with ASD.

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Biological implications of genetic variations in autism spectrum disorders from genomics studies

Bioscience Reports ◽

10.1042/bsr20210593 ◽

2021 ◽

Author(s):

Yue Zhang ◽

Xuanshi Liu ◽

Ruolan Guo ◽

Wenjian Xu ◽

Qi Guo ◽

...

Keyword(s):

Autism Spectrum Disorders ◽

Molecular Genetic ◽

Genetic Diagnosis ◽

Gene Mutations ◽

Autism Spectrum ◽

Repetitive Behaviors ◽

Current Evidence ◽

Restricted Interests ◽

Coding Regions ◽

Spectrum Disorders

Autism spectrum disorders (ASD) is a highly heterogeneous neurodevelopmental condition characterized by atypical social interaction and communication together with repetitive behaviors and restricted interests. The prevalence of ASD has been increased these years. Compelling evidence has shown that genetic factors contribute largely to the development of ASD. However, knowledge about its genetic etiology and pathogenesis is limited. Broad applications of genomics studies have revealed the importance of gene mutations at protein-coding regions as well as the interrupted non-coding regions in the development of ASD. In this review, we summarize the current evidence for the known molecular genetic basis and possible pathological mechanisms as well as the risk genes and loci of ASD. Functional studies for the underlying mechanisms are also implicated. The understanding of the genetics and genomics of ASD is important for the genetic diagnosis and intervention for this condition.

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Neurobiology of Autism Spectrum Disorders

European Psychiatry ◽

10.1016/j.eurpsy.2017.01.199 ◽

2017 ◽

Vol 41 (S1) ◽

pp. S45-S46

Author(s):

T.M. Sheldrick-Michel ◽

B.T. Morten ◽

B. Niels ◽

I. Mirolyuba

Keyword(s):

Autism Spectrum Disorders ◽

High Throughput Screening ◽

Drug Testing ◽

Developmental Stages ◽

Disease Model ◽

Behavioral Flexibility ◽

Autism Spectrum ◽

Spectrum Disorders

Autism Spectrum Disorders (ASD) is a group of neurodevelopmental disorders with heterogeneous etiology characterized by deficits in social cognition, communication, and behavioral flexibility. Disturbances on molecular and cellular level in early brain development incl. intercellular communication, an unbalanced ratio between certain neuronal populations and maturation/differentiation process, oxidative stress, happening in embryonal stages, might be promising candidates to explain the development of autistic symptoms.In order to get a deeper understanding of these processes, valid “disease models” are pivotal. A new cutting edge technique, named brain organoids, has been highlighted as a promising candidate for obtaining a better “disease model”.Brain organoids derived from patients induced pluripotent stem cells (iPSC) follow in vivo timeline development; they also have the ability to recreate the right complexity of the brains, developmental stages. On the cellular and gene expression level, organoids demonstrate a high similarity to the developing brain in vivo and can therefore recapitulate early stages of the neurogenesis. To date organoids are the most relevant cellular in vitro platform for the understanding of the mechanisms behind ADS pathology. Investigations of “mini brains” at different time points in their development will give a wider and more detailed picture of the disease dynamic and thus the development of therapeutic and prevention strategies. It is a tool that can be used for effective high throughput screening of chemical compounds as potential drugs (“in sphero” drug testing). Organoids are a good modeling system for elucidating the role of epigenetic and environmental factors for development of ASD.Disclosure of interestThe authors declare that they have no competing interest.

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MECP2 duplication and mutations impair NSCs differentiation via miR-197 regulated ADAM10

10.1101/312983 ◽

2018 ◽

Author(s):

Yu-Meng Wang ◽

Yu-Fang Zheng ◽

Si-Yu Yang ◽

Zhang-Min Yang ◽

Lin-Na Zhang ◽

...

Keyword(s):

Autism Spectrum Disorders ◽

Notch Signaling ◽

Ectopic Expression ◽

Notch Pathway ◽

Autism Spectrum ◽

Embryonic Brain ◽

Missense Mutations ◽

Spectrum Disorders

AbstractHow MECP2 (Methyl-CpG-binding protein 2) duplication affects cortex development remains elusive. We found that elevated MeCP2 expression promotes neurogenesis during cortex development in Tg(MECP2) mouse brain. Ectopic expression of MeCP2 in NPCs inhibits ADAM10 and hence compromises the NOTCH pathway during NPC differentiation. MeCP2 up-regulates miR-197 to down-regulate ADAM10. The enhanced NPC differentiation/migration in Tg(MECP2) embryonic brain can be repressed by overexpression of ADAM10 or a miR-197 inhibitor.Consistently, the reduced neurogenesis induced by three rare MeCP2 missense mutations (H371R, E394K, G428S) identified in a Han Chinese autism spectrum disorders (ASD) cohort, can be reversed by miR-197 both in vitro and in vivo. Our results revealed that a regulatory axis involving MeCP2, miR-197, ADAM10, and NOTCH signaling is critical for neurogenesis, which is affected by both MeCP2 duplication and mutation.

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Parental Perceptions and Support Needs on Restricted and Repetitive Behaviors for Students with Autism Spectrum Disorders

Journal of Special Education ◽

10.31863/jse.2019.04.35.1.95 ◽

2019 ◽

Vol 35 (1) ◽

pp. 95-126

Author(s):

Jonghee Lee

Keyword(s):

Autism Spectrum Disorders ◽

Autism Spectrum ◽

Parental Perceptions ◽

Repetitive Behaviors ◽

Support Needs ◽

Restricted And Repetitive Behaviors ◽

Students With Autism ◽

Spectrum Disorders

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Region-specific elevations of glutamate + glutamine correlate with the sensory symptoms of autism spectrum disorders

Translational Psychiatry ◽

10.1038/s41398-021-01525-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jason L. He ◽

Georg Oeltzschner ◽

Mark Mikkelsen ◽

Alyssa Deronda ◽

Ashley D. Harris ◽

...

Keyword(s):

Autism Spectrum Disorders ◽

Strong Support ◽

Empirical Support ◽

Brain Regions ◽

Autism Spectrum ◽

Resonance Spectroscopy ◽

Primary Sensorimotor Cortex ◽

Spectrum Disorders ◽

Inhibitory Signaling

AbstractIndividuals on the autism spectrum are often reported as being hyper- and/or hyporeactive to sensory input. These sensory symptoms were one of the key observations that led to the development of the altered excitation-inhibition (E-I) model of autism, which posits that an increase ratio of excitatory to inhibitory signaling may explain certain phenotypical expressions of autism spectrum disorders (ASD). While there has been strong support for the altered E-I model of autism, much of the evidence has come from animal models. With regard to in-vivo human studies, evidence for altered E-I balance in ASD come from studies adopting magnetic resonance spectroscopy (MRS). Spectral-edited MRS can be used to provide measures of the levels of GABA + (GABA + macromolecules) and Glx (glutamate + glutamine) in specific brain regions as proxy markers of inhibition and excitation respectively. In the current study, we found region-specific elevations of Glx in the primary sensorimotor cortex (SM1) in ASD. There were no group differences of GABA+ in either the SM1 or thalamus. Higher levels of Glx were associated with more parent reported difficulties of sensory hyper- and hyporeactivity, as well as reduced feed-forward inhibition during tactile perception in children with ASD. Critically, the finding of elevated Glx provides strong empirical support for increased excitation in ASD. Our results also provide a clear link between Glx and the sensory symptoms of ASD at both behavioral and perceptual levels.

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