scholarly journals The Gut-Brain Axis in Autism Spectrum Disorder: A Focus on the Metalloproteases ADAM10 and ADAM17

2020 ◽  
Vol 22 (1) ◽  
pp. 118
Author(s):  
Yuanpeng Zheng ◽  
Tessa A. Verhoeff ◽  
Paula Perez Pardo ◽  
Johan Garssen ◽  
Aletta D. Kraneveld
Keyword(s):  
Autism Spectrum Disorder ◽  
Intestinal Tract ◽  
Synapse Formation ◽  
Inflammatory Responses ◽  
Repetitive Behavior ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Protein Substrates ◽  
Specific Proteins ◽  
Membrane Bound

Autism Spectrum Disorder (ASD) is a spectrum of disorders that are characterized by problems in social interaction and repetitive behavior. The disease is thought to develop from changes in brain development at an early age, although the exact mechanisms are not known yet. In addition, a significant number of people with ASD develop problems in the intestinal tract. A Disintegrin And Metalloproteases (ADAMs) include a group of enzymes that are able to cleave membrane-bound proteins. ADAM10 and ADAM17 are two members of this family that are able to cleave protein substrates involved in ASD pathogenesis, such as specific proteins important for synapse formation, axon signaling and neuroinflammation. All these pathological mechanisms are involved in ASD. Besides the brain, ADAM10 and ADAM17 are also highly expressed in the intestines. ADAM10 and ADAM17 have implications in pathways that regulate gut permeability, homeostasis and inflammation. These metalloproteases might be involved in microbiota-gut–brain axis interactions in ASD through the regulation of immune and inflammatory responses in the intestinal tract. In this review, the potential roles of ADAM10 and ADAM17 in the pathology of ASD and as targets for new therapies will be discussed, with a focus on the gut–brain axis.

Possibility that the Onset of Autism Spectrum Disorder is Induced by Failure of the Glutamine-Glutamate Cycle

2020 ◽  
Vol 14 (2) ◽  
pp. 170-174
Author(s):  
Koichi Kawada ◽  
Nobuyuki Kuramoto ◽  
Seisuke Mimori
Keyword(s):  
Autism Spectrum Disorder ◽  
Endoplasmic Reticulum ◽  
Environmental Factors ◽  
Endoplasmic Reticulum Stress ◽  
Synapse Formation ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Neurodevelopmental Disease ◽  
Number Of Patients ◽  
The Brain

: Autism spectrum disorder (ASD) is a neurodevelopmental disease, and the number of patients has increased rapidly in recent years. The causes of ASD involve both genetic and environmental factors, but the details of causation have not yet been fully elucidated. Many reports have investigated genetic factors related to synapse formation, and alcohol and tobacco have been reported as environmental factors. This review focuses on endoplasmic reticulum stress and amino acid cycle abnormalities (particularly glutamine and glutamate) induced by many environmental factors. In the ASD model, since endoplasmic reticulum stress is high in the brain from before birth, it is clear that endoplasmic reticulum stress is involved in the development of ASD. On the other hand, one report states that excessive excitation of neurons is caused by the onset of ASD. The glutamine-glutamate cycle is performed between neurons and glial cells and controls the concentration of glutamate and GABA in the brain. These neurotransmitters are also known to control synapse formation and are important in constructing neural circuits. Theanine is a derivative of glutamine and a natural component of green tea. Theanine inhibits glutamine uptake in the glutamine-glutamate cycle via slc38a1 without affecting glutamate; therefore, we believe that theanine may prevent the onset of ASD by changing the balance of glutamine and glutamate in the brain.

scholarly journals 2288 Neural correlates of face processing in autism spectrum disorder: A quantitative meta-analysis of current literature and future directions

2018 ◽  
Vol 2 (S1) ◽  
pp. 21-22
Author(s):  
Carla J. Ammons ◽  
Mary-Elizabeth Winslett ◽  
Rajesh K. Kana
Keyword(s):  
Autism Spectrum Disorder ◽  
Face Processing ◽  
Repetitive Behavior ◽  
Autism Spectrum ◽  
Small Sample ◽  
Spectrum Disorder ◽  
Future Research ◽  
Healthy Controls ◽  
Specific Level

OBJECTIVES/SPECIFIC AIMS: Autism spectrum disorder (ASD) affects 1 in 68 people and includes restricted, repetitive behavior, and social communication deficits. Aspects of face processing (i.e., identity, emotion perception) are impaired in some with ASD. Neuroimaging studies have shown aberrant patterns of brain activation and connectivity of face processing regions. However, small sample sizes and inconsistent results have hindered clinical utility of these findings. The study aims to establish consistent patterns of brain responses to faces in ASD and provide directions for future research. METHODS/STUDY POPULATION: Neuroimaging studies were identified through a multi-database search according to PRISMA guidelines. In total, 23 studies were retained for a sample size of 383 healthy controls and 345 ASD. Peak coordinates were extracted for activation likelihood estimation (ALE) in GingerALE v2.3.6. Follow-up ALE analyses investigated directed Versus undirected gaze, static Versus dynamic, emotional Versus neutral, and familiar Versus unfamiliar faces. RESULTS/ANTICIPATED RESULTS: Faces produced bilateral activation of the fusiform gyrus (FG) in healthy controls (−42 −52 −20; 22 −74 −12, p<0.05, FDR) and left FG activation in ASD (−42 −54 −16, p<0.05, FDR). Activation in both groups was lateral to the mid-fusiform sulcus. Follow-up results pending. DISCUSSION/SIGNIFICANCE OF IMPACT: Reduced right FG activation to faces may inform biomarker or response to intervention studies. Mid-fusiform sulcus proved a reliable predictor of functional divides should be investigated on a subject-specific level.

scholarly journals Periventricular white matter abnormalities and restricted repetitive behavior in autism spectrum disorder

2016 ◽  
Vol 10 ◽  
pp. 36-45 ◽  
Author(s):  
Karen Blackmon ◽  
Emma Ben-Avi ◽  
Xiuyuan Wang ◽  
Heath R. Pardoe ◽  
Adriana Di Martino ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
White Matter ◽  
Repetitive Behavior ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Periventricular White Matter ◽  
White Matter Abnormalities

scholarly journals SOME BIOCHEMICAL IMPLICATIONS IN AUTISM SPECTRUM DISORDER

2014 ◽  
Vol 2 (3) ◽  
Author(s):  
Cristiane Pinheiro Lázaro ◽  
Milena Pereira Pondé ◽  
Luiz Erlon A. Rodrigues
Keyword(s):  
Autism Spectrum Disorder ◽  
Repetitive Behavior ◽  
Clinical Manifestations ◽  
Laboratory Diagnosis ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Physiological Processes ◽  
Oppositional Defiant ◽  
Enzymatic Regulation ◽  
Nosological Entity

Autism spectrum disorder (ASD) affects 0.6 to 1% of the population worldwide. It is characterized by a deficit in communication and social interaction, and is associated with restricted and repetitive behavior patterns. Stereotypes include inflexible adhesion to specific non-functional routines and rituals and a persistent concern with parts of objects rather than the object as a whole. Up to the present time, there are no specific tests that permit a laboratory diagnosis of the disorder to be carried out, and the syndrome is confirmed by clinical observation in the first 36 months of the patient’s life. Clinical manifestations such as epilepsy, mental retardation, sleep disorders, hyperactivity, irritability and auto- and heteroaggressiveness may alter the patient’s prognosis. Around 50% of children with ASD fulfill the criteria for attention deficit hyperactivity disorder (ADHD). Symptoms of oppositional defiant disorder (ODD) associated with autism appear to indicate a distinct phenotype requiring specific therapeutic measures. ASD is not a discrete nosological entity but, rather, a multifactorial syndrome associated with different phenotypic and biological presentations. Various disorders such as pathologies of the gastrointestinal tract have been linked to ASD, not only insofar as causality is concerned but also with respect to their role in aggravating the disease. Other associated disorders include lesions in physiological processes such as the redox metabolism, mitochondrial dysfunction and enzymatic regulation of essential metabolites. Currently, studies on direct and indirect markers of mitochondrial metabolism associated with anomalies found in the brain of these patients point to the possibility of these markers being used as tools with which to reach a diagnosis that would be laboratory based rather than merely clinical.

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.

Corollary Discharge Signaling and Repetitive Behavior in Children With Autism Spectrum Disorder

2020 ◽  
Vol 87 (9) ◽  
pp. S117
Author(s):  
Beier Yao ◽  
Christopher McLaughlin ◽  
Emily Isenstein ◽  
Sylvia Guillory ◽  
Hannah Grosman ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Repetitive Behavior ◽  
Children With Autism ◽  
Autism Spectrum ◽  
Corollary Discharge ◽  
Spectrum Disorder
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