The Role of Genetics, Epigenetics, and the Environment in ASD: A Mini Review

Khogeer, Asim; AboMansour, Iman S; Mohammed, Dia A.

doi:10.3390/epigenomes6020015

Cited by 14 publications

(5 citation statements)

References 114 publications

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“…This anticonvulsant drug is widely employed as an inducer of ASD in animal models across various species [7][8][9][10]. Consistent with findings in autistic humans, exposure to VPA during embryogenesis in zebrafish, is associated with behavioral, neuroanatomical, and genetic alterations, along with deficits in neuronal connectivity and neurotransmitter expression [11][12][13][14][15]. The zebrafish model of ASD offers methodological advantages, including high socialization within the species, prolific reproductive performance, a broad behavioral repertoire, physiological and genetic homology, and neuroanatomical similarity to mammalian species, including humans [13].…”

Section: Introductionmentioning

confidence: 71%

Effect of Enriched Environment on Cerebellum and Social Behavior of Valproic Zebrafish

Flores-Prieto,

Caycho-Salazar,

Manzo

et al. 2024

Preprint

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The etiology of Autism Spectrum Disorder (ASD) has been linked to both genetic and epigenetic factors. Among the epigenetic factors, exposure to valproic acid (VPA), an antiepileptic and mood-modulating drug, has been shown to induce characteristic traits of ASD when exposed during embryogenesis. Conversely, in animal models, Enriched Environment (EE) has demonstrated positive behavioral and neural effects, suggesting its potential as a complementary treatment to pharmacological approaches in central nervous system disorders. In this study, we utilized zebrafish to model ASD characteristics induced by VPA and hypothesized that sensory stimulation through EE could ameliorate the behavioral and neuroanatomical features associated with ASD. To test this hypothesis, we assessed social behavior, cerebellar volume, and Purkinje cell populations via histology and immunohistochemistry after exposing the fish to EE. The results revealed that zebrafish exposed to VPA exhibited social deficits, reduced cerebellar cortex volume, and a decrease in c-Fos-positive cells in the Purkinje layer. In contrast, VPA-exposed fish treated with EE showed increased socialization, augmented cerebellar cortex volume, and an elevation in c-Fos-positive Purkinje cells. These findings suggest that alterations induced by VPA may be ameliorated through EE treatment, highlighting the potential therapeutic impact of sensory stimulation in conditions related to ASD.

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Section: Introductionmentioning

confidence: 71%

Effect of Enriched Environment on Cerebellum and Social Behavior of Valproic Zebrafish

Flores-Prieto,

Caycho-Salazar,

Manzo

et al. 2024

Preprint

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“…For instance, DNA methylation changes in the oxytocin receptor gene have been linked to social deficits in individuals with ASD [ 12 ]. Similarly, alterations in gene expression involved in regulating the stress response have been linked to anxiety and depression in individuals with ASD [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Improving Functional Abilities in Children and Adolescents with Autism Spectrum Disorder Using Non-Invasive REAC Neuro Psycho Physical Optimization Treatments: A PEDI-CAT Study

Rinaldi

Martins²,

Oliveira³

et al. 2023

JPM

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Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder that affects communication, social interaction, and behavior. Non-invasive neuromodulation techniques, such as radioelectric asymmetric conveyer (REAC) technology, have gained attention for their potential to improve the endogenous bioelectric activity (EBA) and neurobiological processes underlying ASD. Neuro Postural Optimization (NPO) and Neuro Psycho Physical Optimization (NPPO) treatments are non-invasive and painless neuromodulation treatments that utilize REAC technology and have shown promising results in improving the symptoms of ASD. This study aimed to evaluate the effects of NPO and NPPO treatments on functional abilities in children and adolescents with ASD using the Pediatric Evaluation of Disability Inventory-Computer Adaptive Test (PEDI-CAT). The study consisted of 27 children and adolescents with ASD who underwent a single session of NPO followed by 18 sessions of NPPO treatment over a period of one week. The results showed significant improvements in the children’s and adolescents’ functional abilities across all domains of the PEDI-CAT. These findings suggest that NPO and NPPO may be effective treatments for improving functional abilities in children and adolescents with ASD.

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“…Recent studies using microarrays, whole-exome sequencing, and whole-genome sequencing have identified that rare de novo mutations as well as variations in single nucleotide polymorphisms are associated with ASD [ 3 , 4 , 5 ]. However, a consensus is emerging that the total fraction of ASD attributable to genetic inheritance may only be 40–60% [ 6 , 7 ]. Apart from a component of genetic heritability in the pathogenesis of ASD, epigenetic and environmental factors are also known to play an important role [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

“…However, a consensus is emerging that the total fraction of ASD attributable to genetic inheritance may only be 40–60% [ 6 , 7 ]. Apart from a component of genetic heritability in the pathogenesis of ASD, epigenetic and environmental factors are also known to play an important role [ 7 , 8 ]. Environmental exposure to toxic chemicals has also been implicated in the etiology of ASD [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Thioredoxin 1 and Thioredoxin Reductase 1 Redox System Is Dysregulated in Neutrophils of Subjects with Autism: In Vitro Effects of Environmental Toxicant, Methylmercury

Alshehri,

Ahmad,

Albekairi

et al. 2023

Toxics

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Autism spectrum disorder (ASD) is a complex developmental disorder in children that results in abnormal communicative and verbal behaviors. Exposure to heavy metals plays a significant role in the pathogenesis or progression of ASD. Mercury compounds pose significant risk for the development of ASD as children are more exposed to environmental toxicants. Increased concentration of mercury compounds has been detected in different body fluids/tissues in ASD children, which suggests an association between mercury exposure and ASD. Thioredoxin1 (Trx1) and thioredoxin reductase1 (TrxR1) redox system plays a crucial role in detoxification of oxidants generated in different immune cells. However, the effect of methylmercury and the Nrf2 activator sulforaphane on the Trx1/TrxR1 antioxidant system in neutrophils of ASD subjects has not been studied previously. Therefore, this study examined the effect of methylmercury on Trx1/TrxR1 expression, TrxR activity, nitrotyrosine, and ROS in neutrophils of ASD and TDC subjects. Our study shows that Trx1/TrxR1 protein expression is dysregulated in ASD subjects as compared to the TDC group. Further, methylmercury treatment significantly inhibits the activity of TrxR in both ASD and TDC groups. Inhibition of TrxR by mercury is associated with upregulation of the Trx1 protein in TDC neutrophils but not in ASD neutrophils. Furthermore, ASD neutrophils have exaggerated ROS production after exposure to methylmercury, which is much greater in magnitude than TDC neutrophils. Sulforaphane reversed methylmercury-induced effects on neutrophils through Nrf2-mediated induction of the Trx1/TrxR1 system. These observations suggest that exposure to the environmental toxicant methylmercury may elevate systemic oxidative inflammation due to a dysregulated Trx1/TrxR1 redox system in the neutrophils of ASD subjects, which may play a role in the progression of ASD.

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The Role of Genetics, Epigenetics, and the Environment in ASD: A Mini Review

Cited by 14 publications

References 114 publications

Effect of Enriched Environment on Cerebellum and Social Behavior of Valproic Zebrafish

Effect of Enriched Environment on Cerebellum and Social Behavior of Valproic Zebrafish

Improving Functional Abilities in Children and Adolescents with Autism Spectrum Disorder Using Non-Invasive REAC Neuro Psycho Physical Optimization Treatments: A PEDI-CAT Study

Thioredoxin 1 and Thioredoxin Reductase 1 Redox System Is Dysregulated in Neutrophils of Subjects with Autism: In Vitro Effects of Environmental Toxicant, Methylmercury

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