Valproic acid and Propionic acid modulated mechanical pathways associated with Autism Spectrum Disorder at prenatal and neonatal exposure

2021 ◽  
Vol 20 ◽  
Author(s):  
Amit Raj Sharma ◽  
Gitika Batra ◽  
Lokesh Saini ◽  
Saurabh Sharma ◽  
Abhishek Mishra ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Valproic Acid ◽  
Nervous System ◽  
Environmental Factors ◽  
Vitamin A ◽  
Brain Development ◽  
Developmental Stage ◽  
Autism Spectrum ◽  
Molecular Pathways ◽  
Food Preservative

: Autism Spectrum Disorder (ASD) is a composite disorder of brain development with uncertain etiology and pathophysiology. Genetic factors are important in ASD causation, although environmental factors are also involved in ASD pathophysiology. Environmental factors might affect the genetic processes of brain development through the modulation of molecular pathways that might be involved with ASD. Valproic acid and Propionic acid are the major environmental factors that serve as medicine and food preservative. VPA is used as an anti-epileptic medicine, but it has adverse effects on pregnant women and alters the developmental patterns of the embryo. It is a multi-targeting agent and affects through the 5-HT, GABA, etc. PPA is a secondary metabolite of gut microbiota that is commonly used as a food preservative. PPA plays a significant role in ASD causation by altering the several developmental molecular pathways like PTEN/Akt, mTOR/Gskβ, Cytokines activated pathways, etc., at the prenatal and neonatal stage. Moreover, ASD complexity might be increased by some other important factors like vitamin A deficiency and Vitamin A is important for cortical brain development and neuronal cell differentiation. Additionally, several important genes such as RELN, Lhx2, CREB, IL-6, NMDA, BDNF, etc. also altered in ASD that involved in brain development, Central Nervous System, Enteric Nervous System. These genes affect the neuronal differentiation, hyperactivity, oxidative stress, oxytocin, and GABA imbalance that lead the improper behavior in autistic individuals. These genes are also studied in VPA and PPA ASD-like animal models. In this review, we explored the mechanical pathways that might be altered with VPA and PPA exposures at the embryonic developmental stage or neonatal developmental stage.

scholarly journals Alterations in the autonomic nerve activities of prenatal autism model mice treated with valproic acid at different developmental stages

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yoshiyuki Kasahara ◽  
Chihiro Yoshida ◽  
Kana Nakanishi ◽  
Miyabi Fukase ◽  
Arisa Suzuki ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Nervous System ◽  
Developmental Stage ◽  
Nervous Activity ◽  
Autism Spectrum ◽  
Parasympathetic Activity ◽  
Autonomic Nerve ◽  
Autonomic Nervous Activity ◽  
Autonomic Nervous ◽  
Sympathetic Nervous

Abstract Autism spectrum disorder (ASD) is characterized by impairment of social communication, repetitive behavior and restrictive interest. The risk of ASD is strongly associated with the prenatal period; for instance, the administration of valproic acid (VPA) to pregnant mothers increases risk of ASD in the child. Patients with ASD often exhibit an alteration in the autonomic nervous system. In this study, we assessed the autonomic nervous activity at each prenatal developmental stage of model mice of ASD treated with VPA, to clarify the relationship between timing of exposure and ASD symptoms. The assessment of the autonomic nervous activity was performed based on the analysis of electrocardiography data collected from fetal and adult mice. Interestingly, VPA model mouse fetuses exhibited a significantly lower activity of the sympathetic nervous system. In contrast, sympathetic nervous activity at P0 was significantly higher. In adult VPA model mice, the parasympathetic activity of female VPA mice was suppressed. Moreover, female VPA mice showed reduced the parasympathetic activity after exposure to restraint stress. These results suggest that the autonomic nervous activity of VPA model mice was altered from the fetal stage, and that the assessment of autonomic nervous activities at an early developmental stage could be useful for the understanding of ASD.

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 Preliminary Results Regarding Sleep in a Zebrafish Model of Autism Spectrum Disorder

2021 ◽  
Vol 11 (5) ◽  
pp. 556
Author(s):  
Madalina Andreea Robea ◽  
Alin Ciobica ◽  
Alexandrina-Stefania Curpan ◽  
Gabriel Plavan ◽  
Stefan Strungaru ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Valproic Acid ◽  
Social Behavior ◽  
Antiepileptic Drug ◽  
Alternative Model ◽  
Neurological Diseases ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Zebrafish Model ◽  
Developmental Defects

Autism spectrum disorder (ASD) is one of the most salient developmental neurological diseases and remarkable similarities have been found between humans and model animals of ASD. A common method of inducing ASD in zebrafish is by administrating valproic acid (VPA), which is an antiepileptic drug that is strongly linked with developmental defects in children. In the present study we replicated and extended the findings of VPA on social behavior in zebrafish by adding several sleep observations. Juvenile zebrafish manifested hyperactivity and an increase in ASD-like social behaviors but, interestingly, only exhibited minimal alterations in sleep. Our study confirmed that VPA can generate specific ASD symptoms, indicating that the zebrafish is an alternative model in this field of research.

On the Development of VR and AR Learning Contents for Children on the Autism Spectrum

2018 ◽  
pp. 106-141 ◽  
Author(s):  
Gerardo Herrera ◽  
Lucia Vera ◽  
Javier Sevilla ◽  
Cristina Portalés ◽  
Sergio Casas
Keyword(s):  
Autism Spectrum Disorder ◽  
Brain Development ◽  
Case Studies ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Important Case ◽  
New Developments ◽  
Group A ◽  
Visually Based ◽  
Educational Contents

Autism spectrum disorder (ASD) is an umbrella term used to group a range of brain development disorders. The learning profile of most people with ASD is mainly visual, and VR and AR technologies offer important advantages to provide a visually based mean for gaining access to educational contents. The prices of VR and AR glasses and helmets have fallen. Also, a number of tools that facilitate the development and publication of AR and VR contents have recently appeared. Therefore, a scenario of opportunity for new developments has appeared in this field. This chapter offers guidelines for developing AR and VR learning contents for people on the autism spectrum and analyses those guidelines from the perspective of two important case studies developed in previous years.

scholarly journals Autism spectrum disorder at the crossroad between genes and environment: contributions, convergences, and interactions in ASD developmental pathophysiology

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Cristina Cheroni ◽  
Nicolò Caporale ◽  
Giuseppe Testa
Keyword(s):  
Autism Spectrum Disorder ◽  
Environmental Factors ◽  
Neurodevelopmental Disorders ◽  
Chemical Exposure ◽  
Autism Spectrum ◽  
Synaptic Function ◽  
Spectrum Disorder ◽  
Regulatory Pathways ◽  
Genes And Environment ◽  
Analytical Approaches

Abstract The complex pathophysiology of autism spectrum disorder encompasses interactions between genetic and environmental factors. On the one hand, hundreds of genes, converging at the functional level on selective biological domains such as epigenetic regulation and synaptic function, have been identified to be either causative or risk factors of autism. On the other hand, exposure to chemicals that are widespread in the environment, such as endocrine disruptors, has been associated with adverse effects on human health, including neurodevelopmental disorders. Interestingly, experimental results suggest an overlap in the regulatory pathways perturbed by genetic mutations and environmental factors, depicting convergences and complex interplays between genetic susceptibility and toxic insults. The pervasive nature of chemical exposure poses pivotal challenges for neurotoxicological studies, regulatory agencies, and policy makers. This highlights an emerging need of developing new integrative models, including biomonitoring, epidemiology, experimental, and computational tools, able to capture real-life scenarios encompassing the interaction between chronic exposure to mixture of substances and individuals’ genetic backgrounds. In this review, we address the intertwined roles of genetic lesions and environmental insults. Specifically, we outline the transformative potential of stem cell models, coupled with omics analytical approaches at increasingly single cell resolution, as converging tools to experimentally dissect the pathogenic mechanisms underlying neurodevelopmental disorders, as well as to improve developmental neurotoxicology risk assessment.

The role of Pax6 in brain development and its impact on pathogenesis of autism spectrum disorder

2019 ◽  
Vol 1705 ◽  
pp. 95-103 ◽  
Author(s):  
Takako Kikkawa ◽  
Cristine R. Casingal ◽  
Seung Hee Chun ◽  
Hiroshi Shinohara ◽  
Kotaro Hiraoka ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Brain Development ◽  
Autism Spectrum ◽  
Spectrum Disorder
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