scholarly journals Disrupted Mitochondrial Network Drives Deficits of Learning and Memory in a Mouse Model of FOXP1 Haploinsufficiency

Genes ◽  
2022 ◽  
Vol 13 (1) ◽  
pp. 127
Author(s):  
Jing Wang ◽  
Gudrun A. Rappold ◽  
Henning Fröhlich
Keyword(s):  
Learning And Memory ◽  
Memory Performance ◽  
Neurodevelopmental Disorder ◽  
Repetitive Behavior ◽  
Underlying Mechanism ◽  
Autism Spectrum ◽  
Global Developmental Delay ◽  
Mitochondrial Network ◽  
Restricted Interests ◽  
Reduced Activity

Reduced cognitive flexibility, characterized by restricted interests and repetitive behavior, is associated with atypical memory performance in autism spectrum disorder (ASD), suggesting hippocampal dysfunction. FOXP1 syndrome is a neurodevelopmental disorder characterized by ASD, language deficits, global developmental delay, and mild to moderate intellectual disability. Strongly reduced Foxp1 expression has been detected in the hippocampus of Foxp1+/− mice, a brain region required for learning and memory. To investigate learning and memory performance in these animals, fear conditioning tests were carried out, which showed impaired associative learning compared with wild type (WT) animals. To shed light on the underlying mechanism, we analyzed various components of the mitochondrial network in the hippocampus. Several proteins regulating mitochondrial biogenesis (e.g., Foxo1, Pgc-1α, Tfam) and dynamics (Mfn1, Opa1, Drp1 and Fis1) were significantly dysregulated, which may explain the increased mitophagy observed in the Foxp1+/− hippocampus. The reduced activity of complex I and decreased expression of Sod2 most likely increase the production of reactive oxygen species and the expression of the pre-apoptotic proteins Bcl-2 and Bax in this tissue. In conclusion, we provide evidence that a disrupted mitochondrial network and the resulting oxidative stress in the hippocampus contribute to the altered learning and cognitive impairment in Foxp1+/− mice, suggesting that similar alterations also play a major role in patients with FOXP1 syndrome.

Specialized Diet Therapies: Exploration for Improving Behavior in Autism Spectrum Disorder (ASD)

2020 ◽  
Vol 27 (40) ◽  
pp. 6771-6786
Author(s):  
Geir Bjørklund ◽  
Nagwa Abdel Meguid ◽  
Maryam Dadar ◽  
Lyudmila Pivina ◽  
Joanna Kałużna-Czaplińska ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Neurodevelopmental Disorder ◽  
Caloric Intake ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Nutritional Deficiencies ◽  
Childhood And Adolescence ◽  
Restricted Interests ◽  
Balanced Diet ◽  
The Individual

As a major neurodevelopmental disorder, Autism Spectrum Disorder (ASD) encompasses deficits in communication and repetitive and restricted interests or behaviors in childhood and adolescence. Its etiology may come from either a genetic, epigenetic, neurological, hormonal, or an environmental cause, generating pathways that often altogether play a synergistic role in the development of ASD pathogenesis. Furthermore, the metabolic origin of ASD should be important as well. A balanced diet consisting of the essential and special nutrients, alongside the recommended caloric intake, is highly recommended to promote growth and development that withstand the physiologic and behavioral challenges experienced by ASD children. In this review paper, we evaluated many studies that show a relationship between ASD and diet to develop a better understanding of the specific effects of the overall diet and the individual nutrients required for this population. This review will add a comprehensive update of knowledge in the field and shed light on the possible nutritional deficiencies, metabolic impairments (particularly in the gut microbiome), and malnutrition in individuals with ASD, which should be recognized in order to maintain the improved socio-behavioral habit and physical health.

scholarly journals CHD8 regulates gut epithelial cell function and affects autism-related behaviours through the gut-brain axis

2021 ◽  
Author(s):  
Ipsita Chaterjee ◽  
Dmitriy Getselter ◽  
Nasreen Ghaneem ◽  
Shai Bel ◽  
Evan Elliott
Keyword(s):  
Epithelial Cells ◽  
Cell Function ◽  
Neurodevelopmental Disorder ◽  
Repetitive Behavior ◽  
Autism Spectrum ◽  
Direct Role ◽  
Tuft Cells ◽  
Core Symptoms ◽  
The Relationship ◽  
Specific Deletion

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by early onset deficits in social behavior and repetitive behavior. Chromodomain helicase DNA binding protein (CHD8) is one of the genes with the strongest association to autism. Alongside with the core symptoms of ASD, individuals with ASD are reported to have gastrointestinal (GI) problems, and a majority of individuals with CHD8 mutations display GI problems. However, the relationship between autism related genes, such as CHD8, gastrointestinal function, and autism related behaviours are yet very unclear. In the current study, we found that mice haploinsufficient for CHD8 have leaky gut, a dysregulated transcriptome in gut epithelial cells, decreased gut tuft cells and goblet cells, and an increase in microbial load. Specific deletion of CHD8 in gut epithelial cells induced an increase in anxiety-related behaviours in, a phenotype that is often observed in autism and full body knockdown of CHD8, in addition to decreased tuft cells. In addition, antibiotic treatment of CHD8 haploinsufficient mice attenuates sociability deficits. Therefore, the current study determines a pathway for autism-related GI deficits, and how these deficits may play a direct role in the development of autism-related behaviours.

scholarly journals Complete Dental Management of an Autism and Intellectual Disability Patient under General Anaesthesia: A Case Report

2021 ◽  
Vol 55 (8) ◽  
Author(s):  
Karin Nadia Firsty ◽  
Nailur Rahmy Wahdany ◽  
Dian Lupita Sari ◽  
Yesri Sasmita Purba ◽  
Tania Saskianti ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
General Anaesthesia ◽  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Recurrent Pain ◽  
Restricted Interests ◽  
Posterior Teeth ◽  
Dental Management ◽  
Left Posterior ◽  
Patient Cooperation

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by persistent deficits in social communication and the presence of restricted interests and repetitive behaviours. Comorbidities following ASD, such as seizure, intellectual disability, and sensory impairment worsen patients’ ability to care for themselves. We present the case of a 22-year-old man with autism, intellectual disability and visual impairment who had recurrent pain in his upper and lower left posterior teeth that had cavities. On the first visit, the patient was observed and had panoramic x-ray. Clinical examination could not be done properly due to lack of patient cooperation. Restoration, pulp capping, tooth extraction, and odontectomy were planned under general anaesthesia.

Early Life Origins of ASD and ADHD

2021 ◽  
Author(s):  
Yuelong Ji ◽  
Ramkripa Raghavan ◽  
Xiaobin Wang
Keyword(s):  
Risk Factors ◽  
Early Life ◽  
Neurodevelopmental Disorder ◽  
Repetitive Behavior ◽  
Density Lipoprotein ◽  
Cost Effective ◽  
Autism Spectrum ◽  
Male Dominance ◽  
High Rate ◽  
Shared Risk

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by impairments in social interaction and communication and by the presence of restrictive, repetitive behavior. Attention deficit hyperactivity disorder (ADHD) is another common lifelong neurodevelopmental disorder characterized by three major presentations: predominantly hyperactive/impulsive, predominantly inattentive, and combined. Although ASD and ADHD are different clinical diagnoses, they share various common characteristics, including male dominance, early childhood onset, links to prenatal and perinatal factors, common comorbidity for each other, and, often, persistence into adulthood. They also have both unique and shared risk factors, which originate in early life and have lifelong implications on the affected individuals and families and society. While genetic factors contribute to ASD and ADHD risk, the environmental contribution to ASD and ADHD has been recognized as having potentially equal importance, which raises the hope for early prevention and intervention. Maternal folate levels, maternal metabolic syndrome, and metabolic biomarkers have been associated with the risk of childhood ASD; while maternal high-density lipoprotein, maternal psychosocial stress, and in utero exposure to opioids have been associated with the risk of childhood ADHD. As for shared factors, male sex, preterm birth, placental pathology, and early life exposure to acetaminophen have been associated with both ASD and ADHD. The high rate of comorbidity of ASD and ADHD and their many shared early life risk factors suggest that early identification and intervention of common early life risk factors may be cost-effective to lower the risk of both conditions. Efforts to improve maternal preconception, prenatal, and perinatal health will not only help reduce adverse reproductive and birth outcomes but will also help mitigate the risk of ASD and ADHD associated with those adverse early life events.

scholarly journals Linking Autism Risk Genes to Disruption of Cortical Development

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2500
Author(s):  
Marta Garcia-Forn ◽  
Andrea Boitnott ◽  
Zeynep Akpinar ◽  
Silvia De Rubeis
Keyword(s):  
Large Scale ◽  
Association Studies ◽  
Neurodevelopmental Disorder ◽  
Cortical Development ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Genome Wide Association Studies ◽  
Restricted Interests ◽  
Risk Genes ◽  
Whole Exome

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder characterized by impairments in social communication and social interaction, and the presence of repetitive behaviors and/or restricted interests. In the past few years, large-scale whole-exome sequencing and genome-wide association studies have made enormous progress in our understanding of the genetic risk architecture of ASD. While showing a complex and heterogeneous landscape, these studies have led to the identification of genetic loci associated with ASD risk. The intersection of genetic and transcriptomic analyses have also begun to shed light on functional convergences between risk genes, with the mid-fetal development of the cerebral cortex emerging as a critical nexus for ASD. In this review, we provide a concise summary of the latest genetic discoveries on ASD. We then discuss the studies in postmortem tissues, stem cell models, and rodent models that implicate recently identified ASD risk genes in cortical development.

Distinct Autistic Traits Are Differentially Associated With the Width of the Multisensory Temporal Binding Window

2018 ◽  
Vol 31 (6) ◽  
pp. 523-536 ◽  
Author(s):  
Ayako Yaguchi ◽  
Souta Hidaka
Keyword(s):  
Neurodevelopmental Disorder ◽  
Continuous Distribution ◽  
Autistic Traits ◽  
Autism Spectrum ◽  
Audiovisual Integration ◽  
Autism Spectrum Quotient ◽  
Temporal Binding ◽  
Restricted Interests ◽  
Temporal Binding Window ◽  
And Behavior

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and interaction, and restricted interests and behavior patterns. These characteristics are considered as a continuous distribution in the general population. People with ASD show atypical temporal processing in multisensory integration. Regarding the flash–beep illusion, which refers to how a single flash can be illusorily perceived as multiple flashes when multiple auditory beeps are concurrently presented, some studies reported that people with ASD have a wider temporal binding window and greater integration than typically developed people; others found the opposite or inconsistent tendencies. Here, we investigated the relationships between the manner of the flash–beep illusion and the various dimensions of ASD traits by estimating the degree of typically developed participants’ ASD traits including five subscales using the Autism-Spectrum Quotient. We found that stronger ASD traits of communication and social skill were associated with a wider and narrower temporal binding window respectively. These results suggest that specific ASD traits are differently involved in the particular temporal binding processes of audiovisual integration.

scholarly journals Translational animal models of autism and neurodevelopmental disorders

2012 ◽  
Vol 14 (3) ◽  
pp. 293-305 ◽  
Keyword(s):  
Mouse Models ◽  
De Novo ◽  
Single Gene ◽  
Neurodevelopmental Disorder ◽  
Gene Mutations ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Restricted Interests ◽  
Homologous Genes ◽  
Biological Outcomes

Autism is a neurodevelopmental disorder whose diagnosis is based on three behavioral criteria: unusual reciprocal social interactions, deficits in communication, and stereotyped repetitive behaviors with restricted interests. A large number of de novo single gene mutations and chromosomal deletions are associated with autism spectrum disorders. Based on the strong genetic evidence, mice with targeted mutations in homologous genes have been generated as translational research tools. Mouse models of autism have revealed behavioral and biological outcomes of mutations in risk genes. The field is now poised to employ the most robust phenotypes in the most replicable mouse models for preclinical screening of novel therapeutics.

scholarly journals Catatonia: A Common Cause of Late Regression in Autism

2021 ◽  
Vol 12 ◽  
Author(s):  
Mohammad Ghaziuddin
Keyword(s):  
Age Of Onset ◽  
Neurodevelopmental Disorder ◽  
Functional Decline ◽  
Autism Spectrum ◽  
Short Term ◽  
Restricted Interests ◽  
Term Outcome ◽  
Common Cause ◽  
The Mean ◽  
Motor Abnormalities

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social communication deficits and restricted interests and behaviors which begin very early in life. In about a quarter of cases, the symptoms emerge about 18–24 months after a period of normal development, a phenomenon commonly described as early regression. However, marked functional decline can also occur in persons with autism after a relatively stable childhood. As opposed to early regression, which occurs in normally developing children, late regression occurs typically in adolescents with an established diagnosis of autism. Apart from their occasional mention in the literature, these individuals have not been examined systematically. This Brief Report describes the presentation, comorbidity and short-term outcome of 20 persons with ASD who developed late regression. The mean age of onset of regression was 13 years. One of the earliest symptoms was an increase in obsessive slowing and compulsive rituals. Other symptoms included motor abnormalities, aggression and mood disturbance. The most common comorbid disorder was catatonia occurring in 17 patients. Despite treatment with several modalities, the outcome was often suboptimal. These findings suggest that catatonia is a common cause of late regression in persons with autism. Clinical and research implications are discussed.

scholarly journals Social (Pragmatic) Communication Disorder: Another name for the Broad Autism Phenotype?

Autism ◽  
2019 ◽  
Vol 23 (8) ◽  
pp. 1982-1992 ◽  
Author(s):  
Judy Flax ◽  
Christine Gwin ◽  
Sherri Wilson ◽  
Yuli Fradkin ◽  
Steve Buyske ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Social Communication ◽  
Repetitive Behavior ◽  
Family Members ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Communication Disorder ◽  
Restricted Interests ◽  
Communication Impairment ◽  
Pragmatic Communication

The Diagnostic and Statistical Manual of Mental Disorders’ (5th ed.) Social (Pragmatic) Communication Disorder is meant to capture the social elements of communication dysfunction in children who do not meet autism spectrum disorder criteria. It is unclear whether Social (Pragmatic) Communication Disorder captures these elements without overlapping with Autism Spectrum Disorder or the Diagnostic and Statistical Manual of Mental Disorders’ (5th ed.) Language Disorder. Standardized behavioral assessments administered during a family genetics study were used to evaluate the social communication impairment and the restricted interests and repetitive behaviors in persons with autism spectrum disorder, language impairment, or neither. Social communication impairment and restricted interests and repetitive behavior were significantly correlated in all family members regardless of affection status. Rates of social communication impairment and restricted interests and repetitive behavior were highest in individuals with autism spectrum disorder. One-third of family members with language impairment presented with at least mild/moderate levels of social communication impairment (36.6%) and restricted interests and repetitive behavior (43.3%). A subset of unaffected members also presented with mild/moderate levels of social communication impairment (parents = 10.1%, siblings 11.6%) and restricted interests and repetitive behavior (parents = 14.0%, siblings = 22.1%). The majority of child family members with mild/moderate levels of social communication impairment had similar restricted interest and repetitive behavior levels reflecting criteria representing the Broad Autism Phenotype. These data suggest that social pragmatic communication disorder does not capture the profiles of children who have both social communication impairment and restricted interests and repetitive behavior but are in need of clinical services.

scholarly journals Nuclear Peroxisome Proliferator-Activated Receptors (PPARs) as Therapeutic Targets of Resveratrol for Autism Spectrum Disorder

2019 ◽  
Vol 20 (8) ◽  
pp. 1878 ◽  
Author(s):  
Rita Barone ◽  
Renata Rizzo ◽  
Giovanni Tabbì ◽  
Michele Malaguarnera ◽  
Richard E. Frye ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Neurodevelopmental Disorder ◽  
Repetitive Behavior ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Mitochondrial Fatty Acid ◽  
Peroxisome Proliferator Activated Receptors

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by defective social communication and interaction and restricted, repetitive behavior with a complex, multifactorial etiology. Despite an increasing worldwide prevalence of ASD, there is currently no pharmacological cure to treat core symptoms of ASD. Clinical evidence and molecular data support the role of impaired mitochondrial fatty acid oxidation (FAO) in ASD. The recognition of defects in energy metabolism in ASD may be important for better understanding ASD and developing therapeutic intervention. The nuclear peroxisome proliferator-activated receptors (PPAR) α, δ, and γ are ligand-activated receptors with distinct physiological functions in regulating lipid and glucose metabolism, as well as inflammatory response. PPAR activation allows a coordinated up-regulation of numerous FAO enzymes, resulting in significant PPAR-driven increases in mitochondrial FAO flux. Resveratrol (RSV) is a polyphenolic compound which exhibits metabolic, antioxidant, and anti-inflammatory properties, pointing to possible applications in ASD therapeutics. In this study, we review the evidence for the existing links between ASD and impaired mitochondrial FAO and review the potential implications for regulation of mitochondrial FAO in ASD by PPAR activators, including RSV.

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