Pathophysiology Of Autism Spectrum Disorder Research Articles

Srcap haploinsufficiency induced autistic-like behaviors in mice through disruption of Satb2 expression

Mutations in the SRCAP gene are among the genetic alterations identified in autism spectrum disorders (ASD). However, the pathogenic mechanisms remain unclear. In this study, we demonstrate that Srcap+/- mice manifest deficits in social novelty response, as well as increased repetitive behaviors, anxiety, and impairments in learning and memory. Notably, a reduction in parvalbumin-positive neurons is observed in the retrosplenial cortex (RSC) and dentate gyrus (DG) of these mice. Through RNA sequencing, we identify dysregulation in 27 ASD-related genes in Srcap+/- mice. Specifically, we find that Srcap regulates expression of Satb2 via H2A.z in the promoter. Therapeutic intervention via retro-orbital injection of adeno-associated virus (AAV)-Satb2 in neonatal Srcap+/- mice leads to amelioration of the neurodevelopmental and ASD-like abnormalities. Furthermore, the expression of Satb2 only in the RSC of adolescent mice rectifies social novelty impairments. These results underscore the pivotal role of Srcap in neurodevelopment, by regulating Satb2, providing valuable insights for the pathophysiology of ASD.

The role of the CNTNAP2 gene in the development of autism spectrum disorder

Autism spectrum disorder (ASD) is a neurodevelopmental disorder in which genetic and environmental factors interact in its development. Research suggests that the contactin associated protein 2 (CNTNAP2) gene may play a role in ASD pathophysiology, yet more studies involving human participants and animal models of autism are needed. One such model may be the use of prenatal valproic acid (VPA) model to induce autism-like behaviors in offspring rats. The aim of this study was twofold: (1) to examine the association of the CNTNAP2 gene rs2710102 variant with ASD in children; and (2) to examine the effect of prenatal exposure to VPA on Cntnap2 gene expression in the rat brain. The study included 167 children of European ancestry—81 diagnosed with ASD (20 girls, 61 boys; age 4.9 ± 1.4 years) and 86 controls (44 girls, 42 boys; 5.1 ± 1.2 years). In vivo experiments were conducted in 80 rats (40 with the VPA model of autism), with Cntnap2 gene expression analysis in the amygdala, hippocampus, prefrontal cortex, and cerebellum. Results demonstrated that the frequency of the CNTNAP2 gene rs2710102 GG genotype was significantly higher in children with ASD when compared with controls (33.3 vs 19.8%; OR=2.03, 95%CI [1.004, 4.102], p = 0.035), although, potentially due to bias in cohort selection, in the ASD children this polymorphism did not meet Hardy-Weinberg expectations (χ2 =5.40, p = 0.02). In addition, Cntnap2 gene expression was significantly lower (p < 0.01) in the amygdala and hippocampus of VPA rats when compared with controls, regardless of sex. These results support previous research and provide evidence for the CNTNAP2 gene as a risk factor for ASD.

Systematic review and meta-analysis: multimodal functional and anatomical neural alterations in autism spectrum disorder

BackgroundThis meta-analysis aimed to explore the most robust findings across numerous existing resting-state functional imaging and voxel-based morphometry (VBM) studies on the functional and structural brain alterations in individuals with autism spectrum disorder (ASD).MethodsA whole-brain voxel-wise meta-analysis was conducted to compare the differences in the intrinsic functional activity and gray matter volume (GMV) between individuals with ASD and typically developing individuals (TDs) using Seed-based d Mapping software.ResultsA total of 23 functional imaging studies (786 ASD, 710 TDs) and 52 VBM studies (1728 ASD, 1747 TDs) were included. Compared with TDs, individuals with ASD displayed resting-state functional decreases in the left insula (extending to left superior temporal gyrus [STG]), bilateral anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC), left angular gyrus and right inferior temporal gyrus, as well as increases in the right supplementary motor area and precuneus. For VBM meta-analysis, individuals with ASD displayed decreased GMV in the ACC/mPFC and left cerebellum, and increased GMV in the left middle temporal gyrus (extending to the left insula and STG), bilateral olfactory cortex, and right precentral gyrus. Further, individuals with ASD displayed decreased resting-state functional activity and increased GMV in the left insula after overlapping the functional and structural differences.ConclusionsThe present multimodal meta-analysis demonstrated that ASD exhibited similar alterations in both function and structure of the insula and ACC/mPFC, and functional or structural alterations in the default mode network (DMN), primary motor and sensory regions. These findings contribute to further understanding of the pathophysiology of ASD.

Landscape of NRXN1 Gene Variants in Phenotypic Manifestations of Autism Spectrum Disorder: A Systematic Review.

Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by social communication challenges and repetitive behaviors. Recent research has increasingly focused on the genetic underpinnings of ASD, with the Neurexin 1 (NRXN1) gene emerging as a key player. This comprehensive systematic review elucidates the contribution of NRXN1 gene variants in the pathophysiology of ASD. Methods: The protocol for this systematic review was designed a priori and was registered in the PROSPERO database (CRD42023450418). A risk of bias analysis was conducted using the Joanna Briggs Institute (JBI) critical appraisal tool. We examined various studies that link NRXN1 gene disruptions with ASD, discussing both the genotypic variability and the resulting phenotypic expressions. Results: Within this review, there was marked heterogeneity observed in ASD genotypic and phenotypic manifestations among individuals with NRXN1 mutations. The presence of NRXN1 mutations in this population emphasizes the gene's role in synaptic function and neural connectivity. Conclusion: This review not only highlights the role of NRXN1 in the pathophysiology of ASD but also highlights the need for further research to unravel the complex genetic underpinnings of the disorder. A better knowledge about the multifaceted role of NRXN1 in ASD can provide crucial insights into the neurobiological foundations of autism and pave the way for novel therapeutic strategies.

Increased gene dosage of RFWD2 causes autistic-like behaviors and aberrant synaptic formation and function in mice.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interactions, communication deficits and repetitive behaviors. A study of autistic human subjects has identified RFWD2 as a susceptibility gene for autism, and autistic patients have 3 copies of the RFWD2 gene. The role of RFWD2 as an E3 ligase in neuronal functions, and its contribution to the pathophysiology of ASD, remain unknown. We generated RFWD2 knockin mice to model the human autistic condition of high gene dosage of RFWD2. We found that heterozygous knockin (Rfwd2+/-) male mice exhibited the core symptoms of autism. Rfwd2+/- male mice showed deficits in social interaction and communication, increased repetitive and anxiety-like behavior, and spatial memory deficits, whereas Rfwd2+/- female mice showed subtle deficits in social communication and spatial memory but were normal in anxiety-like, repetitive, and social behaviors. These autistic-like behaviors in males were accompanied by a reduction in dendritic spine density and abnormal synaptic function on layer II/III pyramidal neurons in the prelimbic area of the medial prefrontal cortex (mPFC), as well as decreased expression of synaptic proteins. Impaired social behaviors in Rfwd2+/- male mice were rescued by the expression of ETV5, one of the major substrates of RFWD2, in the mPFC. These findings indicate an important role of RFWD2 in the pathogenesis of autism.

Exploratory Analysis of MicroRNA Alterations in a Neurodevelopmental Mouse Model for Autism Spectrum Disorder and Schizophrenia.

MicroRNAs (miRNAs) play a crucial role in the regulation of gene expression levels and have been implicated in the pathogenesis of autism spectrum disorder (ASD) and schizophrenia (SCZ). In this study, we examined the adult expression profiles of specific miRNAs in the prefrontal cortex (PFC) of a neurodevelopmental mouse model for ASD and SCZ that mimics perinatal pathology, such as NMDA receptor hypofunction, and exhibits behavioral and neurophysiological phenotypes related to these disorders during adulthood. To model the early neuropathogenesis of the disorders, mouse pups were administered subcutaneously with ketamine (30 mg/Kg) at postnatal days 7, 9, and 11. We focused on a set of miRNAs most frequently altered in ASD (miR-451a and miR-486-3p) and in SCZ (miR-132-3p and miR-137-3p) according to human studies. Additionally, we explored miRNAs whose alterations have been identified in both disorders (miR-21-5p, miR-92a-2-5p, miR-144-3p, and miR-146a-5p). We placed particular emphasis on studying the sexual dimorphism in the dynamics of these miRNAs. Our findings revealed significant alterations in the PFC of this ASD- and SCZ-like mouse model. Specifically, we observed upregulated miR-451a and downregulated miR-137-3p. Furthermore, we identified sexual dimorphism in the expression of miR-132-3p, miR-137-3p, and miR-92a-2-5p. From a translational perspective, our results emphasize the potential involvement of miR-92a-2-5p, miR-132-3p, miR-137-3p, and miR-451a in the pathophysiology of ASD and SCZ and strengthen their potential as biomarkers and therapeutic targets of such disorders.

Pathophysiology of autism spectrum disorders and the gut micro biome: A systematic review

Investigating any possible connections between the two and comprehending any potential processes underlying these connections is the main objective of research on the interaction among autism spectrum disorders (ASD) and guts micro biota. In the world, 1 in 160 persons suffers from ASD, a neuro improvement provision. It is increasingly recognized that environmental variables can contribute to the beginning of ASD, even though it has a substantial genetic component. The essential part of the gut micro biota in ASD is extensively researched because GI symptoms are 4 times more general in ASD patients. ASD patients' abnormal synthesis of bacterial metabolites has been shown to go hand in hand with disordered microbiota composition. The physiological processes that gut microbiota may perturb and so contribute to the path physiology of ASD are now being investigated in clinical research as well as preclinical investigations carried out in rats. The early findings point to the immune system, stomach tryptophan metabolism, and the central nervous system (CNS) as potential contributors. Several clinical studies include the use of antibiotics and probiotic among greater counts of studies involving a transplantation of fecal microbiota, showed behavioral improvements. This study's findings highlight the importance of considering the involvement of the physiological course of ASD is influenced by the gut microbiome, even if our understanding of this relationship is still in its infancy.

Neurochemical differences in core regions of the autistic brain: a multivoxel 1H-MRS study in children

Autism spectrum disorder (ASD) is a neurodevelopmental condition which compromises various cognitive and behavioural domains. The understanding of the pathophysiology and molecular neurobiology of ASD is still an open critical research question. Here, we aimed to address ASD neurochemistry in the same time point at key regions that have been associated with its pathophysiology: the insula, hippocampus, putamen and thalamus. We conducted a multivoxel proton magnetic resonance spectroscopy (1H-MRS) study to non-invasively estimate the concentrations of total choline (GPC + PCh, tCho), total N-acetyl-aspartate (NAA + NAAG, tNAA) and Glx (Glu + Gln), presenting the results as ratios to total creatine while investigating replication for ratios to total choline as a secondary analysis. Twenty-two male children aged between 10 and 18 years diagnosed with ASD (none with intellectual disability, in spite of the expected lower IQ) and 22 age- and gender-matched typically developing (TD) controls were included. Aspartate ratios were significantly lower in the insula (tNAA/tCr: p = 0.010; tNAA/tCho: p = 0.012) and putamen (tNAA/tCr: p = 0.015) of ASD individuals in comparison with TD controls. The Glx ratios were significantly higher in the hippocampus of the ASD group (Glx/tCr: p = 0.027; Glx/tCho: p = 0.011). Differences in tNAA and Glx indices suggest that these metabolites might be neurochemical markers of region-specific atypical metabolism in ASD children, with a potential contribution for future advances in clinical monitoring and treatment.

Photoacoustic viscoelasticity assessment of prefrontal cortex and cerebellum in normal and prenatal valproic acid-exposed rats

Mechanical properties of brain tissues are from principal features from different points of view; diagnosis, the performance of the brain and neurological disorders. Particularly viscoelastic properties of the brain tissues are determinative. In this study based on a proposed accurate and non-invasive method, we have measured the viscoelastic properties of prefrontal cortex and cerebellum, two important brain regions involved in motor learning and pathophysiology of autism spectrum disorder (ASD). In this regard, using photoacoustic systems, viscoelastic properties of tissues from the cerebellum and prefrontal cortex of normal and prenatal VPA (Valproic acid)-exposed (i.e. autistic-like) offspring rats are measured. Results of our study show that the cerebellums of normal tissues are stiffer than the tissue obtained from autistic-like rats, while the viscoelasticity of the prefrontal cortex of normal tissues is higher than that of autistic ones. The proposed method for the measurement of viscoelastic properties of the brain tissue has the potential not only for the fundamental studies but as a diagnosis technique.

Deficiency of FRMD5 results in neurodevelopmental dysfunction and autistic-like behavior in mice.

The pathophysiology of autism spectrum disorders (ASDs) is causally linked to postsynaptic scaffolding proteins, as evidenced by numerous large-scale genomic studies [1, 2] and in vitro and in vivo neurobiological studies of mutations in animal models [3, 4]. However, due to the distinct phenotypic and genetic heterogeneity observed in ASD patients, individual mutation genes account for only a small proportion (<2%) of cases [1, 5]. Recently, a human genetic study revealed a correlation between de novo variants in FERM domain-containing-5 (FRMD5) and neurodevelopmental abnormalities [6]. In this study, we demonstrate that deficiency of the scaffolding protein FRMD5 leads to neurodevelopmental dysfunction and ASD-like behavior in mice. FRMD5 deficiency results in morphological abnormalities in neurons and synaptic dysfunction in mice. Frmd5-deficient mice display learning and memory dysfunction, impaired social function, and increased repetitive stereotyped behavior. Mechanistically, tandem mass tag (TMT)-labeled quantitative proteomics revealed that FRMD5 deletion affects the distribution of synaptic proteins involved in the pathological process of ASD. Collectively, our findings delineate the critical role of FRMD5 in neurodevelopment and ASD pathophysiology, suggesting potential therapeutic implications for the treatment of ASD.

A robust microbiome signature for autism spectrum disorder across different studies using machine learning

Autism spectrum disorder (ASD) is a highly complex neurodevelopmental disorder characterized by deficits in sociability and repetitive behaviour, however there is a great heterogeneity within other comorbidities that accompany ASD. Recently, gut microbiome has been pointed out as a plausible contributing factor for ASD development as individuals diagnosed with ASD often suffer from intestinal problems and show a differentiated intestinal microbial composition. Nevertheless, gut microbiome studies in ASD rarely agree on the specific bacterial taxa involved in this disorder. Regarding the potential role of gut microbiome in ASD pathophysiology, our aim is to investigate whether there is a set of bacterial taxa relevant for ASD classification by using a sibling-controlled dataset. Additionally, we aim to validate these results across two independent cohorts as several confounding factors, such as lifestyle, influence both ASD and gut microbiome studies. A machine learning approach, recursive ensemble feature selection (REFS), was applied to 16S rRNA gene sequencing data from 117 subjects (60 ASD cases and 57 siblings) identifying 26 bacterial taxa that discriminate ASD cases from controls. The average area under the curve (AUC) of this specific set of bacteria in the sibling-controlled dataset was 81.6%. Moreover, we applied the selected bacterial taxa in a tenfold cross-validation scheme using two independent cohorts (a total of 223 samples—125 ASD cases and 98 controls). We obtained average AUCs of 74.8% and 74%, respectively. Analysis of the gut microbiome using REFS identified a set of bacterial taxa that can be used to predict the ASD status of children in three distinct cohorts with AUC over 80% for the best-performing classifiers. Our results indicate that the gut microbiome has a strong association with ASD and should not be disregarded as a potential target for therapeutic interventions. Furthermore, our work can contribute to use the proposed approach for identifying microbiome signatures across other 16S rRNA gene sequencing datasets.

Social Behavior in Animal Models of Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by social deficits and stereotyped, repetitive patterns of behaviors, limited interests, and cognitive impairment. Especially, social deficit has been considered a core feature of ASD. Because of the limitations of the experimental approach in humans, valid animal models are essential in an effort to identify novel therapeutics for social deficits in ASD. The genetic and environmental factors are clinically relevant to the pathophysiology of ASD. Epidemiological studies demonstrate environmental interventions such as prenatal exposure to valproic acid (VPA). Prenatal exposure to VPA represents a robust model of ASD exhibiting face, construct, and predictive validity. Here, we introduce protocols of the social interaction test and the three-chamber test for evaluating social deficits in mice prenatally exposed to VPA.

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.

Gut Microbiota and Autism Spectrum Disorders: An Overview of Correlations and Potential Implications for Therapeutic Interventions

Gut Microbiota and Autism Spectrum Disorders: An Overview of Correlations and Potential Implications for Therapeutic Interventions Abstract: At the beginning of research on microbiota, researchers focused mainly on the role of microbiota dysbiosis in the development of gastrointestinal diseases. However, over the last years, researchers have also identified correlations with other physical processes and neuropsychiatric diseases such as autism spectrum disorder. These correlations are believed to be at least partly mediated through the brain-gut-microbiome axis. An altered composition of microbiota in patients with autism spectrum disorder was detected compared to healthy controls. Today, the discussion centers around a possible systemic impact of the metabolites of some microbiota or microbiota-induced chronic inflammatory processes on the brain (mediated through the brain-gut-microbiome axis) as an underlying mechanism. Still, the specific underlying mechanisms remain largely unknown, so conclusions on therapeutic implications are difficult to determine. Here, we describe some promising approaches to improving autistic behavior through dietary changes, the use of prebiotics and probiotics, stool transplantation from healthy controls, and restricted absorbance of certain metabolites. We need further clinical studies of high quality to fully understand the pathophysiology of autism spectrum disorder and to improve diagnostic and therapeutic strategies.

Impact of IDO activation and alterations in the kynurenine pathway on hyperserotonemia, NAD+ production, and AhR activation in autism spectrum disorder

Hyperserotonemia is the most replicated biochemical anomaly associated with autism spectrum disorder (ASD) and has been reported in 35–46% of individuals with ASD. Serotonin is synthesised from the essential amino acid tryptophan (TRP). However, the main catabolic route of TRP is the kynurenine pathway (KP), which competes with serotonin synthesis when indoleamine dioxygenase (IDO) is activated. Using the same cohort of individuals with ASD, we used to report extensive studies of the serotonin/melatonin pathway, and found increased kynurenine (KYN), suggesting IDO activation in 58.7% of individuals with ASD (159/271), supported by a strong negative correlation between KYN/TRP ratio and miR-153-3p plasma levels, which negatively regulates IDO. IDO activation was associated with normoserotonemia, suggesting that IDO activation could mask hyperserotonemia which meant that hyperserotonemia, if not masked by IDO activation, could be present in ~94% of individuals with ASD. We also identified several KP alterations, independent of IDO status. We observed a decrease in the activity of 3-hydroxyanthranilate dioxygenase which translated into the accumulation of the aryl hydrocarbon receptor (AhR) selective ligand cinnabarinic acid, itself strongly positively correlated with the AhR target stanniocalcin 2. We also found a deficit in NAD+ production, the end-product of the KP, which was strongly correlated with plasma levels of oxytocin used as a stereotypical neuropeptide, indicating that regulated neuropeptide secretion could be limiting. These results strongly suggest that individuals with ASD exhibit low-grade chronic inflammation that is mediated in most cases by chronic AhR activation that could be associated with the highly prevalent gastrointestinal disorders observed in ASD, and explained IDO activation in ~58% of the cases. Taken together, these results extend biochemical anomalies of TRP catabolism to KP and posit TRP catabolism as a possible major component of ASD pathophysiology.

Possible roles of deep cortical neurons and oligodendrocytes in the neural basis of human sociality.

Sociality is an instinctive property of organisms that live in relation to others and is a complex characteristic of higher order brain functions. However, the evolution of the human brain to acquire higher order brain functions, such as sociality, and the neural basis for executing these functions and their control mechanisms are largely unknown. Several studies have attempted to evaluate how human sociality was acquired during the course of evolution and the mechanisms controlling sociality from a neurodevelopment viewpoint. This review discusses these findings in the context of human brain evolution and the pathophysiology of autism spectrum disorder (ASD). Comparative genomic studies of postmortem primate brains have demonstrated human-specific regulatory mechanisms underlying higher order brain functions, providing evidence for the contribution of oligodendrocytes to human brain function. Functional analyses of the causative genes of ASD in animal models have demonstrated that the neural basis of social behavior is associated with layer 6 (L6) of the neocortex and oligodendrocytes. These findings demonstrate that both neurons and oligodendrocytes contribute to the neural basis and molecular mechanisms underlying human brain evolution and social functioning. This review provides novel insights into sociability and the corresponding neural bases of brain disorders and evolution.

Lipid Peroxidation via Regulating the Metabolism of Docosahexaenoic Acid and Arachidonic Acid in Autistic Behavioral Symptoms.

The association between the lipid peroxidation product malondialdehyde (MDA)-modified low-density lipoprotein (MDA-LDL) and the pathophysiology of autism spectrum disorder (ASD) is unclear. This association was studied in 17 children with ASD and seven age-matched controls regarding autistic behaviors. Behavioral symptoms were assessed using the Aberrant Behavior Checklist (ABC). To compensate for the small sample size, adaptive Lasso was used to increase the likelihood of accurate prediction, and a coefficient of variation was calculated for suitable variable selection. Plasma MDA-LDL levels were significantly increased, and plasma SOD levels were significantly decreased in addition to significantly increased plasma docosahexaenoic acid (DHA) levels and significantly decreased plasma arachidonic acid (ARA) levels in the 17 subjects with ASD as compared with those of the seven healthy controls. The total ABC scores were significantly higher in the ASD group than in the control group. The results of multiple linear regression and adaptive Lasso analyses revealed an association between increased plasma DHA levels and decreased plasma ARA levels, which were significantly associated with total ABC score and increased plasma MDA-LDL levels. Therefore, an imbalance between plasma DHA and ARA levels induces ferroptosis via lipid peroxidation. Decreased levels of α-linolenic acid and γ-linolenic acid may be connected to the total ABC scores with regard to lipid peroxidation.

Non-synaptic function of the autism spectrum disorder-associated gene SYNGAP1 in cortical neurogenesis.

Genes involved in synaptic function are enriched among those with autism spectrum disorder (ASD)-associated rare genetic variants. Dysregulated cortical neurogenesis has been implicated as a convergent mechanism in ASD pathophysiology, yet it remains unknown how 'synaptic' ASD risk genes contribute to these phenotypes, which arise before synaptogenesis. Here, we show that the synaptic Ras GTPase-activating (RASGAP) protein 1 (SYNGAP1, a top ASD risk gene) is expressed within the apical domain of human radial glia cells (hRGCs). In a human cortical organoid model of SYNGAP1 haploinsufficiency, we find dysregulated cytoskeletal dynamics that impair the scaffolding and division plane of hRGCs, resulting in disrupted lamination and accelerated maturation of cortical projection neurons. Additionally, we confirmed an imbalance in the ratio of progenitors to neurons in a mouse model of Syngap1 haploinsufficiency. Thus, SYNGAP1-related brain disorders may arise through non-synaptic mechanisms, highlighting the need to study genes associated with neurodevelopmental disorders (NDDs) in diverse human cell types and developmental stages.

Cord Blood Metabolite Profiles and Their Association with Autistic Traits in Childhood.

Autism Spectrum Disorder (ASD) is a diverse neurodevelopmental condition. Gene-environmental interactions in early stages of life might alter metabolic pathways, possibly contributing to ASD pathophysiology. Metabolomics may serve as a tool to identify underlying metabolic mechanisms contributing to ASD phenotype and could help to unravel its complex etiology. In a population-based, prospective cohort study among 783 mother-child pairs, cord blood serum concentrations of amino acids, non-esterified fatty acids, phospholipids, and carnitines were obtained using liquid chromatography coupled with tandem mass spectrometry. Autistic traits were measured at the children's ages of 6 (n = 716) and 13 (n = 648) years using the parent-reported Social Responsiveness Scale. Lower cord blood concentrations of SM.C.39.2 and NEFA16:1/16:0 were associated with higher autistic traits among 6-year-old children, adjusted for sex and age at outcome. After more stringent adjustment for confounders, no significant associations of cord blood metabolites and autistic traits at ages 6 and 13 were detected. Differences in lipid metabolism (SM and NEFA) might be involved in ASD-related pathways and are worth further investigation.

“Comparative evaluation of different chemical agents induced Autism Spectrum Disorder in experimental Wistar rats”

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition with uncertain etiology and pathophysiology. Several studies revealed that the commonly used animal models like Valproic Acid (VPA) and Propionic Acid (PPA) do not precisely represent the disease as the human patient does. The current study was conducted on different chemically (VPA, PPA, Poly I:C, Dioxin (2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)) & Chlorpyrifos (CPF)) induced ASD-like animal models and validated the best suitable experimental animal model, which would closely resemble with clinical features of the ASD. This validated model might help to explore the pathophysiology of ASD. This study included rat pups prenatally exposed to VPA, PPA, Poly I:C, Dioxin & CPF within GD9 to GD15 doses. The model groups were validated through developmental and behavioral parameters, Gene Expressions, Oxidative Stress, and Pro-inflammatory and Anti-inflammatory cytokines levels. Developmental and neurobehavioral parameters showed significant changes in model groups compared to the control. In oxidative stress parameters and neuro-inflammatory cytokines levels, model groups exhibited high oxidative stress and neuro-inflammation compared to control groups. Gene expression profile of ASD-related genes showed significant downregulation in model groups compared to the control group. Moreover, the Poly I:C group showed more significant results than other model groups. The comparison of available ASD-like experimental animal models showed that the Poly I:C induced model represented the exact pathophysiology of ASD as the human patient does. Poly I:C was reported in the maternal immune system activation via the inflammatory cytokines pathway, altering embryonic development and causing ASD in neonates.