Etiopathogenesis Of Autism Spectrum Disorder Research Articles

Serum BAFF, APRIL, TWEAK, TNFSF18, TNFR2, and TNFRS12A levels in preschool children with autism spectrum disorder

Objectives A gradually increasing number of studies have reported that dysregulation in the immune system may be a contributing factor in the etiopathogenesis of autism spectrum disorder (ASD). However, only limited data has existed about the role of tumor necrosis factor (TNF) superfamily members in ASD. This study aimed to investigate whether serum levels of BAFF, APRIL, TWEAK, TNFSF18 TNFR2, and TNFRS12A are associated with ASD in preschool children. Methods A total of 65 (52 boys/13 girls) preschool children with ASD and 40 (28 boys/12 girls) healthy controls were included in the study. The severity of the ASD symptoms was assessed by the Autism Behavior Checklist and the Childhood Autism Rating Scale. Serum levels of immunologic parameters were measured by enzyme-linked immunosorbent assay. Results Analysis indicated that serum BAFF, TNFSF18, TNFR2, and TNFRS12A levels were significantly lower and serum APRIL and TWEAK levels were significantly higher in the ASD group than in the control group. However, with logistic regression only low BAFF levels and high APRIL levels had relationships with the presence of ASD. Conclusions These findings suggest that TNF superfamily members, especially the BAFF/APRIL system may play a role in the pathophysiology of ASD.

Comparison of HMGB1, RAGE, TLR4, and NF-κB levels in children and adolescents diagnosed with autism spectrum disorder with healthy controls

Introduction The objective of our study is to clarify the involvement of the HMGB1/RAGE/TLR4/NF-kB axis, a crucial component in inflammation, in the etiopathogenesis of autism spectrum disorder (ASD). Method We analyzed the levels of HMGB1, RAGE, TLR4, and NF-kB in serum from 80 children (40 with ASD and 40 controls). All participants’ sociodemographic characteristics were recorded. In order to determine the severity of the disorder, the Aberrant Behavior Checklist, Childhood Autism Rating Scale, and Autism Behavior Checklist were administered to the ASD group. Result While the soluble TLR4 level was significantly higher in the ASD group (p < 0.001), other parameters examined did not show significant differences between groups. Furthermore, soluble TLR4 serum level was positively correlated with Problem Behavior Checklist hyperactivity subscale scores (p = 0.031), and RAGE serum level was negatively correlated with ABC Stereotype score (p = 0.001). Discussion It was thought that serum TLR4 levels may be important in the etiology of ASD. TLR4 levels are linked to symptoms like hyperactivity in autism, which suggests that this parameter could be used as a clinical guide. Further research is required to substantiate our discoveries and to clarify the involvement of HMGB1, RAGE, TLR4, and NF-kB in the etiopathogenesis of ASD.

Role of Glia Cells in Autism Spectrum Disorders

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with an increasing frequency, manifested by functional disorders in social communication and social interaction, limited interests, and repetitive behaviors. The etiology of autism spectrum disorder has not yet been fully elucidated and there are many areas that need further study. Increasing studies have shown that disruptions in synaptic functions are critical in the onset of ASD. Glial cells have a role in the regulation of synaptic functions. In ASD, changes are seen in the number of neurons and glia cells in the affected cerebral cortex, and these changes cause dysregulation in synaptic functions and affect behaviors. Studies provide information about the role of glia cells in the pathophysiology of ASD, but more data is needed on the relationship between ASD and glia cells. In this review, the importance of glial cells in the etiopathogenesis of ASD and studies will be discussed.

Association of ABCA13 Gene Variants with Autism Spectrum Disorder and Other Neuropsychiatric Disorders

Introduction: Autism spectrum disorder (ASD) is a neuropsychiatric disorder characterized by impaired social skills and limited or repetitive behaviors. In this study, we investigated the role of the ABCA13 gene in the etiopathogenesis of ASD. Methods: Single-nucleotide variants were evaluated in 79 ASD patients (59 males +20 females) with no established genetic etiology associated with ASD using whole-exome sequencing/clinical exome sequencing method. Family segregation analysis was performed using Sanger sequencing. We presented the clinical and genetic findings of these cases and their parents in detail. Results: We presented 10 different ABCA13 gene variants in cases with ASD and 10 parents carrying the same ABCA13 gene variant. There of these variants were likely pathogenic and seven variants were classified as variant of uncertain significance. Our cases had a comorbidity rate for attention deficit hyperactivity disorder (ADHD) as 70%. Various types of neuropsychiatric symptoms and diagnoses were detected including ADHD, anxiety disorder, intellectual disability, delay in speech, and febrile convulsion among the parents. Conclusion: To date, very few variants have been reported in the ABCA13 gene. Our findings enrich the role of ABCA13 gene may play a common role in the landscape of neuropsychiatric disorders.

Celiac disease in autism spectrum disorder: data from an Italian child cohort

BackgroundIn recent decades some studies described the frequent co-occurrence of celiac disease autoimmunity and overt celiac disease in patients with autism. Therefore, it was suggested that celiac disease could play a possible role in the etiopathogenesis of autism spectrum disorder. However, several other studies have not confirmed this association. The aim of the present study was to elucidate the potential association between autism spectrum disorder and celiac disease.MethodsWe prospectively collected data from an Italian cohort of 223 children at the time of their clinical diagnosis of autism spectrum disorder in the 2019–2020 period. A serological celiac disease screening was performed and data were available for 196 patients; male (M):female (F) ratio = 4.4:1; median age = 3.6 years; age range = 1.6–12.8 years. Full-blown celiac disease was established according to the diagnostic algorithm of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) 2012 or 2019 guidelines. Fisher’s exact test was used to compare the celiac disease seroprevalence and prevalence in our autism spectrum disorder cohort and in the Italian healthy pediatric population studied by Gatti et al. to highlight the possible differences between the two groups.ResultsA not statistically significant difference between the celiac disease seroprevalence in our autism spectrum disorder cohort (4.08%) and Gatti’s Italian healthy group (2.22%) was found, p = 0.0810; OR = 1.871. A similar result emerged for overt celiac disease prevalences (2.24% versus 1.58%, respectively), p = 0.2862; OR = 1.431.ConclusionsOur data validates a weakness of association between autism spectrum disorder and celiac disease. On the basis of our results, a regular screening for CD in patients with ASD is not recommended to a greater extent than in the general population.

Evaluation of procalcitonin and C-reactive protein levels in children with autism spectrum disorder and attention deficit hyperactivity disorder

Inflammation is thought to play a role in the etiopathogenesis of autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Procalcitonin (PCT) is an inflammatory biomarker released by thyroid parafollicular cells. CRP is systemic biomarker of inflammation. In this study, the hypothesis that PCT and C-reactive protein (CRP) might be indicators of increased inflammatory response was tested. For this purpose, PCT and CRP as well as other simple inflammatory markers were evaluated in children with ASD and ADHD. A total of 33 ASD, 36 ADHD, and 31 healthy controls were included in the study, who were similar in terms of gender and age. PCT, CRP, sedimentation and hemogram parameters (Neutrophil Lymphocyte Ratio) were measured in children aged 5-15 years. PCT and CRP values were found to be statistically significantly higher in ASD and ADHD children compared to healthy controls (p < 0.05). A positive correlation was found between PCT and CRP values (r: 0.358; p < 0.001). No significant correlations were found between disorder severity scale scores and PCT and CRP values (p > 0.05 for both). Accordingly, it is suggested that inflammation plays a role in the etiopathogenesis of these disorders. PCT and CRP may be used as inflammation markers.

Comparison of serum thrombospondin-1 and thrombospondin-2 levels among children with autism spectrum disorder and healthy controls

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder, the etiology of which has not been clearly determined yet. There is increasing evidence that synaptic and dendritic changes are involved in the etiology of ASD. The aim of this study is to determine whether serum Thrombospondin-1 and Thrombospondin-2 differ between ASD patients and healthy controls. This study also investigates possible correlations between clinical symptomatology of ASD and serum Thrombospondin-1 and Thrombospondin-2 levels. Method: A total of 44 children with ASD and 21 healthy controls under 6 years of age were included in the study. Symptom severity and behavioral problems among children with ASD were evaluated by using Childhood Autism Rating Scale and Abnormal Behavior Checklist. Serum levels of Thrombospondin-1 and Thrombospondin-2 were measured by using commercial enzyme-linked immunosorbent assay kits. Result: No statistically significant differences were found between the two groups in terms of serum Thrombospondin-1 and Thrombospondin-2 levels. In addition, no correlation was determined between Thrombospondin-2 levels and clinical symptomatology and severity of ASD. However, the Thrombospondin-1 level was found to negatively correlated with the total score of Childhood Autism Rating Scale, inappropriate speech and stereotype subscale scores of Aberrant Behavior Checklist scale. Conclusion: Thrombospondin-1 might have a potential role in the etiopathogenesis of ASD. Further studies are required to clearly elucidate the association between Trombospondin-1 and ASD.

GARBHOPAGHATAKARA BHAVA, PRECONCEPTIONAL RISK FACTORS FOR AUTISM: A CROSS-SECTIONAL SURVEY

Background: Garbhopaghatakara bhava, inclusive of altered maternal habits, diet, behaviours, and exposures in the perinatal period disrupt normal growth and development of the foetus. Autism spectrum disorders (ASD) are characterized by impaired social behaviour and communication skills. Many risk factors for ASD are identified but with no generalization of definite aetiology. Psychosocial anomalies in Ayurveda have been explained under the spectrum of unmada. Such diseases are said to present early in life and persist throughout the lifespan when associated with garbhopaghatakara bhava. This study explores the association of garbhopaghatakara bhava with the etiopathogenesis of ASD. Materials and Methods: Parents of 50 children who have ASD enquired about garbhopaghatakara bhava using a structured survey format. Results: Male preponderance (80%) with middle socio-economic strata (62%) predominated the study population. 48% had delayed speech and communication with poor eye contact, and 24% with delay in gross motor milestones. Garbhopaghatakara bhava leading to ashaya dushti (structural and functional variation in uterine milieu) were secondary to abortions (22%), hypothyroidism (10%), advanced parental age (64%), diabetes mellitus (8%). Amongst diet and activities in the mother, madhura- katu rasa (22%), eating less (28%), frequent meals (28%), day sleep (42%), night wakening (54%), excess travel (18%) and withhold of urges (16%) were seen. The genetic risk was sporadic (14%). Discussion: Garbhopaghatakara bhava can act by changing the epigenetics or disturbing the nutrition, psyche, and intellectual faculties in the child. Conclusion: Baseline information about the association of garbhopaghatakara bhava with ASD was identified. However, further analytical studies can provide substantial information and evidence.

Assessment of a combination of plasma anti-histone autoantibodies and PLA2/PE ratio as potential biomarkers to clinically predict autism spectrum disorders

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficiencies in social interaction and repetitive behaviors. Multiple studies have reported abnormal cell membrane composition and autoimmunity as known mechanisms associated with the etiopathogenesis of ASD. In this study, multiple regression and combined receiver operating characteristic (ROC) curve as statistic tools were done to clarify the relationship between phospholipase A2 and phosphatidylethanolamine (PE) ratio (PLA2/PE) as marker of lipid metabolism and membrane fluidity, and antihistone-autoantibodies as marker of autoimmunity in the etiopathology of ASD. Furthermore, the study intended to define the linear combination that maximizes the partial area under an ROC curve for a panel of markers. Forty five children with ASD and forty age- and sex-matched controls were enrolled in the study. Using ELISA, the levels of antihistone-autoantibodies, and PLA2 were measured in the plasma of both groups. PE was measured using HPLC. Statistical analyses using ROC curves and multiple and logistic regression models were performed. A notable rise in the area under the curve was detected using combined ROC curve models. Additionally, higher specificity and sensitivity of the combined markers were documented. The present study indicates that the measurement of the predictive value of selected biomarkers related to autoimmunity and lipid metabolism in children with ASD using a ROC curve analysis should lead to a better understanding of the pathophysiological mechanism of ASD and its link with metabolism. This information may enable the early diagnosis and intervention.

Interventions on Microbiota: Where Do We Stand on a Gut-Brain Link in Autism? A Systematic Review.

The alteration of the microbiota–gut–brain axis has been recently recognized as a critical modulator of neuropsychiatric health and a possible factor in the etiopathogenesis of autism spectrum disorders (ASD). This systematic review offers practitioners an overview of the potential therapeutic options to modify dysbiosis, GI symptoms, and ASD severity by modulating the microbiota–gut–brain axis in ASD, taking into consideration limits and benefits from current findings. Comprehensive searches of PubMed, Scopus, the Web of Science Core Collection, and EMBASE were performed from 2000 to 2021, crossing terms referred to ASD and treatments acting on the microbiota–gut–brain axis. A total of 1769 publications were identified, of which 19 articles met the inclusion criteria. Data were extracted independently by two reviewers using a preconstructed form. Despite the encouraging findings, considering the variability of the treatments, the samples size, the duration of treatment, and the tools used to evaluate the outcome of the examined trials, these results are still partial. They do not allow to establish a conclusive beneficial effect of probiotics and other interventions on the symptoms of ASD. In particular, the optimal species, subspecies, and dosages have yet to be identified. Considering the heterogeneity of ASD, double-blind, randomized, controlled trials and treatment tailored to ASD characteristics and host-microbiota are recommended.

ВОЗМОЖНАЯ РОЛЬ ЭССЕНЦИАЛЬНЫХ ЭЛЕМЕНТОВ В ЭТИОПАТОГЕНЕЗЕ РАССТРОЙСТВ АУТИСТИЧЕСКОГО СПЕКТРА И ЗАДЕРЖКИ ПСИХОРЕЧЕВОГО РАЗВИТИЯ У ДЕТЕЙ РАЗНОГО ВОЗРАСТА

An imbalance of trace elements plays a significant role in the etiopathogenesis of Autism Spec-trum Disorder (ASD) and Speech Development Delay (SDD). The aim of the study was to analyze an essential trace elements content in the hair samples of children with ASD and SDD for better understanding age and gender related diversity. The study included 258 children with ASD and 239 children with SDD. Control group consisted of 620 healthy children of similar age. All children were divided into two age categories (1.5 to 3 years old and 4 to 13 years old). It was shown that girls with ASD had more deviations in hair essential trace elements levels than boys. Children with ASD and SDD (1.5 to 3 years old) had significantly decreased hair iodine level (by 48-58%, p &lt; 0.0001). Low iodine level can be a significant indicator of mental and speech development delay. Normalization of hair iodine level in older boys with ASD accompanied by significant decrease in hair cobalt level (by 24%, p = 0.0001) may reflect age-related characteristics of iodine and cobalt metabolism. Low hair manganese level (by 12-44%, p &lt; 0.05) was observed in all groups of children. It’s possibly associated with decreased manganese excretion from the body and can provoke manganese-induced neurotoxicity. The decrease in copper levels in girls of different ages (by 9-17%, p &lt; 0.01) is probably influenced by hormonal status and earlier onset of puberty.

Comparison of Serum VEGF, IGF-1, and HIF-1α Levels in Children with Autism Spectrum Disorder and Healthy Controls.

The aim of this study was to determine whether serum VEGF, IGF-1, and HIF-1α levels differed between Autism Spectrum Disorder (ASD) patients and healthy controls. A total of 40 children with ASD and 40 healthy controls aged 4-12years were included. Serum levels of VEGF, IGF-1, and HIF-1α were measured using commercial enzyme-linked immunosorbent assay kits. Serum IGF-1 levels were found to be statistically significantly higher in the ASD group than in the control group. Serum HIF-1α levels were borderline significantly lower in the ASD group. There was no statistically significant difference in serum VEGF levels between the two groups. IGF-1 and HIF-1α may play a potential role in the etiopathogenesis of ASD.

Investigation the Relationship of Autism Spectrum Disorder and FOXP2, GRIN2B, KATNAL2, GABRA4 Genes.

Introduction:Autism spectrum disorder is a genetically and phenotypically heterogeneous group. Genetic studies carried out to date have suggested that both common and rare genetic variants play a role in the etiology of this disorder. In our study, we aimed to investigate the effect of FOXP2, GRIN2B, KATNAL2 and GABRA4 gene variants in the pathogenesis of autism spectrum disorder.Method:In our prospectively planned study, all exons and exon-intron junctions of FOXP2, GRIN2B, KATNAL2 and GABRA4 genes were screened by next generation sequencing analysis in 96 patients who diagnosed with autism spectrum disorder.Results:In our study, the average age was 10.1 and the male/female ratio was 75/21. Pathogenic or likely pathogenic variants were not detected in FOXP2, GRIN2B, KATNAL2 and GABRA4 genes, however, 69 intronic variants of unknown clinical significance were detected in 50 cases (52%). Among those, 26 were in the GABRA4 gene, 22 in the FOXP2 gene, 13 in the KATNAL2 gene, and 8 in the GRIN2B gene. Twenty three of these 69 variants were novel that were not previously reported in the literature.Conclusion:In our study, we could not identify a relationship between the autism spectrum disorder and FOXP2, GRIN2B, KATNAL2 and GABRA4 genes. Identifying genetic risk factors that play a role in the etiopathogenesis of autism spectrum disorder will contribute significantly to understanding the molecular mechanisms of the disease and the development of new treatment strategies. In this context, comprehensive molecular genetic studies such as whole exome or whole genome sequencing are required with higher number of cases in different populations.

Alteration of the steroidogenesis in boys with autism spectrum disorders

The etiology of autism spectrum disorders (ASD) remains unknown, but associations between prenatal hormonal changes and ASD risk were found. The consequences of these changes on the steroidogenesis during a postnatal development are not yet well known. The aim of this study was to analyze the steroid metabolic pathway in prepubertal ASD and neurotypical boys. Plasma samples were collected from 62 prepubertal ASD boys and 24 age and sex-matched controls (CTRL). Eighty-two biomarkers of steroidogenesis were detected using gas-chromatography tandem-mass spectrometry. We observed changes across the whole alternative backdoor pathway of androgens synthesis toward lower level in ASD group. Our data indicate suppressed production of pregnenolone sulfate at augmented activities of CYP17A1 and SULT2A1 and reduced HSD3B2 activity in ASD group which is partly consistent with the results reported in older children, in whom the adrenal zona reticularis significantly influences the steroid levels. Furthermore, we detected the suppressed activity of CYP7B1 enzyme readily metabolizing the precursors of sex hormones on one hand but increased anti-glucocorticoid effect of 7α-hydroxy-DHEA via competition with cortisone for HSD11B1 on the other. The multivariate model found significant correlations between behavioral indices and circulating steroids. From dependent variables, the best correlation was found for the social interaction (28.5%). Observed changes give a space for their utilization as biomarkers while reveal the etiopathogenesis of ASD. The aforementioned data indicate a direction of the future research with a focus on the expression and functioning of genes associated with important steroidogenic enzymes in ASD patients from early childhood to adrenarche.

Cannabinoids for People with ASD: A Systematic Review of Published and Ongoing Studies

The etiopathogenesis of autism spectrum disorder (ASD) remains largely unclear. Among other biological hypotheses, researchers have evidenced an imbalance in the endocannabinoid (eCB) system, which regulates some functions typically impaired in ASD, such as emotional responses and social interaction. Additionally, cannabidiol (CBD), the non-intoxicating component of Cannabis sativa, was recently approved for treatment-resistant epilepsy. Epilepsy represents a common medical condition in people with ASD. Additionally, the two conditions share some neuropathological mechanisms, particularly GABAergic dysfunctions. Hence, it was hypothesized that cannabinoids could be useful in improving ASD symptoms. Our systematic review was conducted according to the PRISMA guidelines and aimed to summarize the literature regarding the use of cannabinoids in ASD. After searching in Web of KnowledgeTM, PsycINFO, and Embase, we included ten studies (eight papers and two abstracts). Four ongoing trials were retrieved in ClinicalTrials.gov. The findings were promising, as cannabinoids appeared to improve some ASD-associated symptoms, such as problem behaviors, sleep problems, and hyperactivity, with limited cardiac and metabolic side effects. Conversely, the knowledge of their effects on ASD core symptoms is scarce. Interestingly, cannabinoids generally allowed to reduce the number of prescribed medications and decreased the frequency of seizures in patients with comorbid epilepsy. Mechanisms of action could be linked to the excitatory/inhibitory imbalance found in people with ASD. However, further trials with better characterization and homogenization of samples, and well-defined outcomes should be implemented.

Vitamin D Deficiency and Autism Spectrum Disorder.

Vitamin D is a neurosteroid hormone crucially involved in neurodevelopment. Neural cell proliferation, neurotransmission, oxidative stress and immune function represent the main mechanisms mediated by vitamin D in the Central Nervous System. Therefore, its deficiency during pregnancy and early childhood may significantly impact on a developing brain, leading to possible adverse neuropsychological outcomes including Autism Spectrum Disorder (ASD). Significant vitamin D deficiency is described within children affected by ASD and in pregnant mothers whose offspring will later develop ASD, suggesting a possible role of the hormone as a contributing risk factor in the etiopathogenesis of ASD. We reviewed the actual literature on the potential contributing role of prenatal and early postnatal vitamin D deficiency in ASD etiopathogenesis, at both genetic and environmental levels, and the possible effect of vitamin D supplementation in autistic children. Conflicting but promising results emerged on the topic. Further Randomized Controlled Trials studies carried out during pregnancy and early infancy are necessary for better understanding the possible contribution of vitamin D deficiency in the etiopathogenesis of autism and the potential efficacy of the hormone supplementation in the improvement of ASD core symptoms.

Neurotoxicity by mercury is not associated with autism spectrum disorders in Spanish children

BackgroundThe pathophysiological etiologies related with the development of Autism Spectrum Disorders (ASD) remain controversial. Different authors have studied neurotoxins such as mercury (Hg) and their relationship with ADS. The objective of this study was to assess the levels of Hg in hair in a group of ASD children (chronic exposure) and in urinary excretion (acute exposure), in comparison to a healthy group.MethodsA case-control study was conducted in Spanish children. We compared 54 ASD children (aged 2–6) with no other associated pathology to a normally-developing control group (54 subjects).ResultsThere were no differences in urine (p:0.631) and hair (p:1.000) samples percentages below the limits of detection between the control and the ASD groups, and also between patients in the regression ASD subgroup (AMR) (p:0.08) and the non-regression ASD subgroup (ANMR) (p:0.705). When the analysis was adjusted for age and sex, the differences between Hg levels maintained not significant. There were no correlations between Hg concentrations in the ASD group as a whole (p: 0.739), or when they were subdivided into ASD-AMR (p: 0.739) and ASD-ANMR (p: 0.363).ConclusionsThe present study shows no evidence in our geographical area to support an association between mercury neurotoxicity and the etiopathogenesis of ASD.

The role of neuroglia in autism spectrum disorders.

Neuroglia are a large class of neural cells of ectodermal (astroglia, oligodendroglia, and peripheral glial cells) and mesodermal (microglia) origin. Neuroglial cells provide homeostatic support, protection, and defense to the nervous tissue. Pathological potential of neuroglia has been acknowledged since their discovery. Research of the recent decade has shown the key role of all classes of glial cells in autism spectrum disorders (ASD), although molecular mechanisms defining glial contribution to ASD are yet to be fully characterized. This narrative conceptualizes recent findings of the broader roles of glial cells, including their active participation in the control of cerebral environment and regulation of synaptic development and scaling, highlighting their putative involvement in the etiopathogenesis of ASD.

ЭССЕНЦИАЛЬНЫЕ МАКРО- И МИКРОЭЛЕМЕНТЫ В ЭТИОЛОГИИ И ПАТОГЕНЕЗЕ РАССТРОЙСТВА АУТИСТИЧЕСКОГО СПЕКТРА У ДЕТЕЙ

A large number of studies have been conducted up to date associated with the elemental status of children with Autism Spectrum Disorder (ASD). However, it is still difficult to fully explain the relationship between ASD and elements due to previous inconsistent scientific results. The article reviews the possible role of essential elements in the etiopathogenesis of ASD in children. An imbalance of essential elements can cause a disruption in development of central nervous system. It leads to impaired differentiation and proliferation of neurons and disruption in myelination, affects neurochemistry and neurotransmitter balance, provokes oxidative stress and neuroinflammation. In particular, the balance of trace elements such as copper, iron and selenium is necessary to maintain the antioxidant defense systems. Increased levels of free radicals lead to cellular damage, oxidative stress and neuroinflammation linked to ASD. Magnesium and calcium, acting as secondary messengers in the central nervous system (CNS), regulate the processes of neural networks’ maturation and neurotransmitter release. An imbalance of potassium and sodium changes electrical activity of the brain and may be the cause of epileptiform discharges in ASD. Zinc provides the processes of neuronal migration and neurotransmission, while copper, iodine and iron contribute to myelination of nerve fibers.

NRXN1 Deletion and Exposure to Methylmercury Increase Astrocyte Differentiation by Different Notch-Dependent Transcriptional Mechanisms.

Controversial evidence points to a possible involvement of methylmercury (MeHg) in the etiopathogenesis of autism spectrum disorders (ASD). In the present study, we used human neuroepithelial stem cells from healthy donors and from an autistic patient bearing a bi-allelic deletion in the gene encoding for NRXN1 to evaluate whether MeHg would induce cellular changes comparable to those seen in cells derived from the ASD patient. In healthy cells, a subcytotoxic concentration of MeHg enhanced astroglial differentiation similarly to what observed in the diseased cells (N1), as shown by the number of GFAP positive cells and immunofluorescence signal intensity. In both healthy MeHg-treated and N1 untreated cells, aberrations in Notch pathway activity seemed to play a critical role in promoting the differentiation toward glia. Accordingly, treatment with the established Notch inhibitor DAPT reversed the altered differentiation. Although our data are not conclusive since only one of the genes involved in ASD is considered, the results provide novel evidence suggesting that developmental exposure to MeHg, even at subcytotoxic concentrations, induces alterations in astroglial differentiation similar to those observed in ASD.