scholarly journals Pogz deficiency leads to abnormal behavior, transcription dysregulation and impaired cerebellar physiology

2018 ◽  
Author(s):  
Reut Suliman ◽  
Ben Title ◽  
Yahel Cohen ◽  
Maayan Tal ◽  
Nitzan Tal ◽  
...  
Keyword(s):  
Autism Spectrum ◽  
Firing Frequency ◽  
Human Condition ◽  
Conditional Knockout ◽  
Negative Regulator ◽  
Abnormal Behavior ◽  
Chromatin Regulators ◽  
Transcription Dysregulation ◽  
Cerebellar Purkinje Cells ◽  
And Behavior

AbstractGenes implicated in autism spectrum disorder (ASD) are enriched with chromatin regulators, but the mechanisms leading to the abnormal behavior and cognition are still unclear. Animal models are crucial for studying the effects of mutations on brain function and behavior. We generated conditional knockout mice with brain-specific mutation in Pogz, a heterochromatin regulator recurrently mutated in ASD and other neurodevelopmental disorders, and demonstrated that these mice display phenotypes that resemble the human condition. Pogz deficiency led to smaller brain, growth impairment, motor learning deficits, and increased social interactions that mimic the human overly friendly phenotype. At the molecular level, reporter assay indicated that POGZ functions as a negative regulator of transcription through its interaction with HP1 proteins. In accordance, we found a significant upregulation of gene expression, most notably in the cerebellum. Furthermore, Pogz deficiency was associated with a significant reduction in the firing frequency of simple and complex spikes in cerebellar Purkinje cells with no changes in their intrinsic properties. Overall, our findings support a mechanism linking heterochromatin dysregulation to cerebellar circuit dysfunction and to motor and social abnormalities in ASD.

scholarly journals Pogz deficiency leads to transcription dysregulation and impaired cerebellar activity underlying autism-like behavior in mice

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Reut Suliman-Lavie ◽  
Ben Title ◽  
Yahel Cohen ◽  
Nanako Hamada ◽  
Maayan Tal ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Autism Spectrum ◽  
Conditional Knockout ◽  
Gene Set Enrichment Analysis ◽  
Negative Regulator ◽  
Luciferase Reporter ◽  
Motor Deficits ◽  
Knockout Mouse Model ◽  
Deficient Mice

AbstractSeveral genes implicated in autism spectrum disorder (ASD) are chromatin regulators, including POGZ. The cellular and molecular mechanisms leading to ASD impaired social and cognitive behavior are unclear. Animal models are crucial for studying the effects of mutations on brain function and behavior as well as unveiling the underlying mechanisms. Here, we generate a brain specific conditional knockout mouse model deficient for Pogz, an ASD risk gene. We demonstrate that Pogz deficient mice show microcephaly, growth impairment, increased sociability, learning and motor deficits, mimicking several of the human symptoms. At the molecular level, luciferase reporter assay indicates that POGZ is a negative regulator of transcription. In accordance, in Pogz deficient mice we find a significant upregulation of gene expression, most notably in the cerebellum. Gene set enrichment analysis revealed that the transcriptional changes encompass genes and pathways disrupted in ASD, including neurogenesis and synaptic processes, underlying the observed behavioral phenotype in mice. Physiologically, Pogz deficiency is associated with a reduction in the firing frequency of simple and complex spikes and an increase in amplitude of the inhibitory synaptic input in cerebellar Purkinje cells. Our findings support a mechanism linking heterochromatin dysregulation to cerebellar circuit dysfunction and behavioral abnormalities in ASD.

scholarly journals Augmented Reality for Autistic Children to Enhance Their Understanding of Facial Expressions

2021 ◽  
Vol 5 (8) ◽  
pp. 48
Author(s):  
Mohammad Wedyan ◽  
Jannat Falah ◽  
Ryan Alturki ◽  
Irini Giannopulu ◽  
Salsabeel F. M. Alfalah ◽  
...  
Keyword(s):  
Augmented Reality ◽  
Social Interactions ◽  
Facial Expressions ◽  
Computer Technology ◽  
Autism Spectrum ◽  
Human Condition ◽  
Facial Features ◽  
Age Group ◽  
Level Of Education ◽  
And Behavior

Difficulty in understanding the feelings and behavior of other people is considered one of the main symptoms of autism. Computer technology has increasingly been used in interventions with Autism Spectrum Disorder (ASD), especially augmented reality, to either treat or alleviate ASD symptomatology. Augmented reality is an engaging type of technology that helps children interact easily and understand and remember information, and it is not limited to one age group or level of education. This study utilized AR to display faces with six different basic facial expressions—happiness, sadness, surprise, fear, disgust, and anger—to help children to recognize facial features and associate facial expressions with a simultaneous human condition. The most important point of this system is that children can interact with the system in a friendly and safe way. Additionally, our results showed the system enhanced social interactions, talking, and facial expressions for both autistic and typical children. Therefore, AR might have a significant upcoming role in talking about the therapeutic necessities of children with ASD. This paper presents evidence for the feasibility of one of the specialized AR systems.

scholarly journals Neuroanatomy and behavior in mice with a haploinsufficiency of AT-rich interactive domain 1B (ARID1B) throughout development

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
J. Ellegood ◽  
S. P. Petkova ◽  
A. Kinman ◽  
L. R. Qiu ◽  
A. Adhikari ◽  
...  
Keyword(s):  
Corpus Callosum ◽  
Ex Vivo ◽  
Chromatin Modification ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Social Deficits ◽  
Altered Expression ◽  
Developmental Growth ◽  
And Behavior

Abstract Background One of the causal mechanisms underlying neurodevelopmental disorders (NDDs) is chromatin modification and the genes that regulate chromatin. AT-rich interactive domain 1B (ARID1B), a chromatin modifier, has been linked to autism spectrum disorder and to affect rare and inherited genetic variation in a broad set of NDDs. Methods A novel preclinical mouse model of Arid1b deficiency was created and validated to characterize and define neuroanatomical, behavioral and transcriptional phenotypes. Neuroanatomy was assessed ex vivo in adult animals and in vivo longitudinally from birth to adulthood. Behavioral testing was also performed throughout development and tested all aspects of motor, learning, sociability, repetitive behaviors, seizure susceptibility, and general milestones delays. Results We validated decreased Arid1b mRNA and protein in Arid1b+/− mice, with signatures of increased axonal and synaptic gene expression, decreased transcriptional regulator and RNA processing expression in adult Arid1b+/− cerebellum. During neonatal development, Arid1b+/− mice exhibited robust impairments in ultrasonic vocalizations (USVs) and metrics of developmental growth. In addition, a striking sex effect was observed neuroanatomically throughout development. Behaviorally, as adults, Arid1b+/− mice showed low motor skills in open field exploration and normal three-chambered approach. Arid1b+/− mice had learning and memory deficits in novel object recognition but not in visual discrimination and reversal touchscreen tasks. Social interactions in the male–female social dyad with USVs revealed social deficits on some but not all parameters. No repetitive behaviors were observed. Brains of adult Arid1b+/− mice had a smaller cerebellum and a larger hippocampus and corpus callosum. The corpus callosum increase seen here contrasts previous reports which highlight losses in corpus callosum volume in mice and humans. Limitations The behavior and neuroimaging analyses were done on separate cohorts of mice, which did not allow a direct correlation between the imaging and behavioral findings, and the transcriptomic analysis was exploratory, with no validation of altered expression beyond Arid1b. Conclusions This study represents a full validation and investigation of a novel model of Arid1b+/− haploinsufficiency throughout development and highlights the importance of examining both sexes throughout development in NDDs.

scholarly journals Standardized Method for the Assessment of Behavioral Responses of Zebrafish Larvae

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 884
Author(s):  
Hideyuki Maeda ◽  
Noritoshi Fukushima ◽  
Akihiro Hasumi
Keyword(s):  
Early Stage ◽  
Scientific Evidence ◽  
Video Tracking ◽  
Abnormal Behavior ◽  
Laboratory Setting ◽  
Zebrafish Larvae ◽  
Experimental Systems ◽  
Standardized Method ◽  
Life Phenomena ◽  
And Behavior

Zebrafish are easy to breed in a laboratory setting as they are extremely fertile and produce dozens of eggs per set. Because zebrafish eggs and the skin of the early-stage larvae are transparent, their embryos and the hearts and muscles of their larvae can be easily observed. Multiple rapid analyses of heart rate and behavior can be performed on these larvae simultaneously, enabling investigation of the influence of neuroactive substances on abnormal behavior, death, and associated pathogenetic mechanisms. Zebrafish larvae are becoming increasingly popular among researchers and are used in laboratories worldwide to study various vertebrate life phenomena; more experimental systems using zebrafish will undoubtedly be developed in the future. However, based on the available literature, we believe that the conceptualization of a protocol based on scientific evidence is necessary to achieve standardization. We exposed zebrafish larvae at 6–7 days post-fertilization to 50 repeated light–dark stimuli at either 15-min or 5-min intervals. We measured the traveled distance and habituation time through a video tracking apparatus. The traveled distance stabilized after the 16th repetition when the zebrafish were exposed to light–dark stimuli at 15-min intervals and after the 5th repetition when exposed at 5-min intervals. Additionally, at 15-min intervals, the peak of the traveled distance was reached within the first minute in a dark environment, whereas at 5-min intervals, it did not reach the peak even after 5 min. The traveled distance was more stable at 5-min intervals of light/dark stimuli than at 15-min intervals. Therefore, if one acclimatizes zebrafish larvae for 1 h and collects data from the 5th repetition of light/dark stimuli at intervals of 5 min in the light/dark test, a stable traveled distance result can be obtained. The establishment of this standardized method would be beneficial for investigating substances of unknown lethal concentration.

scholarly journals Effects of a postnatal Atrx conditional knockout in neurons on autism-like behaviours in male and female mice

2020 ◽  
Author(s):  
Nicole Martin-Kenny ◽  
Nathalie G. Bérubé
Keyword(s):  
Repeated Measures ◽  
Susceptibility Gene ◽  
Acoustic Startle ◽  
Acoustic Startle Response ◽  
Autism Spectrum ◽  
Conditional Knockout ◽  
Male And Female ◽  
Female Mice ◽  
Excitatory Neurons ◽  
Behavioural Tests

AbstractBackgroundAlpha-thalassemia/mental retardation, X-linked, or ATRX, is an autism susceptibility gene that encodes a chromatin remodeler. Mutations of ATRX result in the ATR-X intellectual disability syndrome and have been identified in autism spectrum disorder (ASD) patients. The mechanisms by which ATRX mutations lead to autism and autistic-like behaviours are not yet known. To address this question, we generated mice with postnatal Atrx inactivation in excitatory neurons of the forebrain and performed a battery of behavioural assays that assess autistic-like behaviours.MethodsMale and female mice with a postnatal conditional knockout of Atrx were tested in a battery of behavioural tests that assess autistic features. We utilized paradigms that measure social behaviour, repetitive and stereotyped behaviours, as well as sensory gating. Statistics were calculated by two-way repeated measures ANOVA with Sidak’s multiple comparison test or unpaired Student’s T-tests as indicated.ResultsThe behaviour tests revealed no significant differences between Atrx-cKO and control mice. We identified sexually dimorphic changes in odor habituation and discrimination; however, these changes did not correlate with social deficits. We additionally observed sex-specific differences in sociability, vertical episodes, and acoustic startle response when results were analyzed by sex.ConclusionThe postnatal knockout of Atrx in forebrain excitatory neurons does not lead to autism-related behaviours in male or female mice.

scholarly journals Influence of adaptive physical education on motor possibilities, behavior and quality of life of children with autism

2020 ◽  
Vol 6 (2) ◽  
pp. 41
Author(s):  
O.V. Musiyenko ◽  
R.V. Chopyk ◽  
N.B. Kizlo
Keyword(s):  
Quality Of Life ◽  
Physical Education ◽  
Motor Skills ◽  
Motor Development ◽  
Self Care ◽  
Children With Autism ◽  
Autism Spectrum ◽  
Adaptive Physical Education ◽  
And Behavior

<p><strong>The </strong><strong>aim</strong> of the work is to establish the impact of adaptive physical education classes according to our proposed method on the motor abilities and behavior of children with autism spectrum disorders and on the quality of life of their families.</p><p><strong>Material and methods</strong>. Analysis and generalization of literature data on the peculiarities of psycho-motor development of children with autism, their behavior. Development of methods of adaptive physical education of children with autism, which includes exercises for the development of general and fine motor skills, imitation, coordination of movements and the development of physical qualities such as strength, agility, flexibility. Expert assessment of test exercises. Questionnaire of parents about the psychophysical condition of their children and the quality of life of families raising a child with autism. Methods of mathematical statistics.</p><p><strong>Results</strong>. It has been established that children with autism have significant impairments of motor activity and psychophysical condition, which significantly affects the quality of life of children and their families. There is a very low level of development of motor skills. Parents of children in the experimental group noted that from now on their children began to have fewer problems with movement, their movements became more coordinated and it became easier to move. In terms of self-care and self-care, the difficulties became less significant (average level), the usual daily activities also became easier, the phenomena of discomfort and anxiety decreased.</p><p><strong>Conclusions</strong>. Children with autism have significant deviations in motor development, arbitrariness of movements, understanding of expediency of movements, general motility of the body. Classes in adaptive physical education according to our proposed method allowed children with autism to overcome most motor disorders, which was a prerequisite for improving higher nervous activity and behavior. Significant improvement of psychophysical condition of children as a result of employment, and also growth of quality of life is established.</p>

scholarly journals The relationship between sleep and behavior in autism spectrum disorder (ASD): a review

2014 ◽  
Vol 6 (1) ◽  
Author(s):  
Simonne Cohen ◽  
Russell Conduit ◽  
Steven W Lockley ◽  
Shantha MW Rajaratnam ◽  
Kim M Cornish
Keyword(s):  
Autism Spectrum Disorder ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
And Behavior ◽  
The Relationship

scholarly journals ASTN2 modulates synaptic strength by trafficking and degradation of surface proteins

2018 ◽  
Vol 115 (41) ◽  
pp. E9717-E9726 ◽  
Author(s):  
Hourinaz Behesti ◽  
Taylor R. Fore ◽  
Peter Wu ◽  
Zachi Horn ◽  
Mary Leppert ◽  
...  
Keyword(s):  
Surface Protein ◽  
Surface Expression ◽  
Autism Spectrum ◽  
Copy Number Variations ◽  
Surface Proteins ◽  
Synaptic Activity ◽  
Synaptic Proteins ◽  
Immunogold Electron Microscopy ◽  
Dynamic Regulation ◽  
Cerebellar Purkinje Cells

Surface protein dynamics dictate synaptic connectivity and function in neuronal circuits. ASTN2, a gene disrupted by copy number variations (CNVs) in neurodevelopmental disorders, including autism spectrum, was previously shown to regulate the surface expression of ASTN1 in glial-guided neuronal migration. Here, we demonstrate that ASTN2 binds to and regulates the surface expression of multiple synaptic proteins in postmigratory neurons by endocytosis, resulting in modulation of synaptic activity. In cerebellar Purkinje cells (PCs), by immunogold electron microscopy, ASTN2 localizes primarily to endocytic and autophagocytic vesicles in the cell soma and in subsets of dendritic spines. Overexpression of ASTN2 in PCs, but not of ASTN2 lacking the FNIII domain, recurrently disrupted by CNVs in patients, including in a family presented here, increases inhibitory and excitatory postsynaptic activity and reduces levels of ASTN2 binding partners. Our data suggest a fundamental role for ASTN2 in dynamic regulation of surface proteins by endocytic trafficking and protein degradation.

Screening and Diagnosis of Autism Spectrum Disorder via Assistive Tools

2022 ◽  
pp. 1-21
Author(s):  
Gurkan Tuna ◽  
Ayşe Tuna
Keyword(s):  
Autism Spectrum Disorder ◽  
Random Forest ◽  
Performance Metrics ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Spectrum Disorder ◽  
K Nearest Neighbors ◽  
Medical Test ◽  
And Behavior

Autism spectrum disorder (ASD) is a challenging developmental condition that involves restricted and/or repetitive behaviors and persistent challenges in social interaction and speech and nonverbal communication. There is not a standard medical test used to diagnose ASD; therefore, diagnosis is made by looking at the child's developmental history and behavior. In recent years, due to the increase in diagnosed cases of ASD, researchers proposed software-based tools to aid in and expedite the diagnosis. Considering the fact that most of these tools rely on the use of classifiers, in study, random forest, decision tree, k-nearest neighbors, and zero rule algorithms are used as classifiers, and their performances are compared using well-known performance metrics. As proven in the study, random forest algorithm can provide higher accuracy than the others in the classification of ASD and can be integrated into a computer- or humanoid-robot-based system for automated prescreening and diagnosis of ASD in preschool children groups.

Sign in / Sign up

Export Citation Format

Share Document