Pathogenesis Of Autism Research Articles

Synaptic Aspects of the Pathogenesis of Autism, Amyotrophic Lateral Sclerosis, and Alzheimer’s Disease

Synaptic Aspects of the Pathogenesis of Autism, Amyotrophic Lateral Sclerosis, and Alzheimer’s Disease

Application Research of Music Therapy in Mental Health of Special Children

A healthy psychological state is the premise for children to carry out various activities. Previous surveys have shown that children with special needs are affected by their own obstacles and are more prone to psychological problems such as sensitivity, low self-esteem, and impulsiveness. Therefore, it is necessary to provide more systematic mental health education support for special children. Mental health education programs are an efficient form of maintaining children’s mental health. However, in the field of special education, the number of mental health education courses developed according to the physical and mental characteristics and developmental needs of special children is relatively small, and there are many difficulties in the implementation process. Autism disorder (ASD) is a kind of pervasive developmental dysfunction that is relatively common and representative in clinical practice. In recent years, the number of autistic children has continued to surge, and has gradually expanded from a family problem to a serious social problem. At present, the evaluation of the effect of autism intervention mainly relies on various behavioral scales, which are subjective to a certain extent. At the same time, due to the unclear pathogenesis of autism, the treatment of autism cannot be predicated on the right medicine, and can only be intervened in various ways. The purpose of this paper is to explore the difference between the EEG signals of autistic children and typically developing control (TD) children through the analysis method of EEG signals, and based on the analysis of EEG signals from an objective point of view, to study whether the music therapy method of Chinese Zither playing training can effectively Improving the brain functional status of children with autism yields positive therapeutic outcomes. The experimental results show that the complexity of brain electrical signals of ASD children is much lower than that of TD children, and there is a significant difference in the brain functional state between the two. The music therapy method based on Chinese zither playing training can improve the brain function of autistic patients, and there is a positive therapeutic effect. And with the extension of the training period, the effect may be more significant. Chinese zither playing training can provide a new direction for the intervention of autism.

Untargeted Metabolomic Analysis Reveals the Metabolic Disturbances and Exacerbation of Oxidative Stress in the Cerebral Cortex of a BTBR Mouse Model of Autism.

The etiology and pathology of autism spectrum disorders (ASDs) are still poorly understood, which largely limit the treatment and diagnosis of ASDs. Emerging evidence supports that abnormal metabolites in the cerebral cortex of a BTBR mouse model of autism are involved in the pathogenesis of autism. However, systematic study on global metabolites in the cerebral cortex of BTBR mice has not been conducted. The current study aims to characterize metabolic changes in the cerebral cortex of BTBR mice by using an untargeted metabolomic approach based on UPLC-Q-TOF/MS. C57BL/6J mice were used as a control group. A total of 14 differential metabolites were identified. Compared with the control group, the intensities of PI(16:0/22:5(4Z,7Z,10Z,13Z,16Z)), PC(22:6(4Z,7Z,10Z,13Z,16Z,19Z)/18:1(9Z)), PA(16:0/18:1(11Z)), 17-beta-estradiol-3-glucuronide, and N6,N6,N6-trimethyl-L-lysine decreased significantly (p < 0.01) and the intensities of 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline, LysoPC(20:4(5Z,8Z,11Z,14Z)/0:0), adenosine monophosphate, adenosine-5'-phosphosulfate, LacCer(d18:1/12:0),3-dehydro-L-gulonate, N-(1-deoxy-1-fructosyl)tryptophan, homovanillic acid, and LPA(0:0/18:1(9Z)) increased significantly (p < 0.01) in the BTBR group. These changes in metabolites were closely related to perturbations in lipid metabolism, energy metabolism, purine metabolism, sulfur metabolism, amino acid metabolism, and carnitine biosynthesis. Notably, exacerbation of the oxidative stress response caused by differential prooxidant metabolites led to alteration of antioxidative systems in the cerebral cortex and resulted in mitochondrial dysfunction, further leading to abnormal energy metabolism as an etiological mechanism of autism. A central role of abnormal metabolites in neurological functions associated with behavioral outcomes and disturbance of sulfur metabolism and carnitine biosynthesis were found in the cerebral cortex of BTBR mice, which helped increase our understanding for exploring the pathological mechanism of autism.

Alterations of presynaptic proteins in autism spectrum disorder.

The expanded use of hypothesis-free gene analysis methods in autism research has significantly increased the number of genetic risk factors associated with the pathogenesis of autism. A further examination of the implicated genes directly revealed the involvement in processes pertinent to neuronal differentiation, development, and function, with a predominant contribution from the regulators of synaptic function. Despite the importance of presynaptic function in synaptic transmission, the regulation of neuronal network activity, and the final behavioral output, there is a relative lack of understanding of the presynaptic contribution to the pathology of autism. Here, we will review the close association among autism-related mutations, autism spectrum disorders (ASD) phenotypes, and the altered presynaptic protein functions through a systematic examination of the presynaptic risk genes relating to the critical stages of synaptogenesis and neurotransmission.

A-138 Investigation of Potential Involvement of The Adrenal Cortex In The Pathogenesis of Autism In Prepubertal Male Jordanian Children

Abstract Objective: The investigation of adrenal steroids and testosterone levels in male autistic children will, undoubtedly, help to elucidate the pathogenetic implication of these hormones in the development of autism and their role as risk factors. The objective of this case-control study is to explore the potential involvement of adrenal steroids in the pathogenesis of autism. Method: Serum levels of total testosterone (TT), dehydroepiandrosterone (DHEA) and sex-hormone binding globulin (SHBG) were measured in 32 Jordanian autistic male patients and in 32 healthy age-matched children. Independent t-test was used to investigate statistical significance in study groups with a (p) value of less than 0.05 was considered significant. Preliminary univariate logistic regression was used to assess which of the measured lab parameters should be included in the final regression models. Multivariable logistic regression (backward stepwise selection) was used in autism risk prediction. Results: TT had a positive strong correlation with DHEA (r=+62, p≤0.001), suggesting an adrenal source of the elevated androgens. The Likelihood of developing autism was increased by 1.03 times for an increase in one ng/dl of DHEA, by 0.92 times for an increase by one nmol/l of SHBG and by only 0.04 times for an increase in one mIU/ml of FSH. Conclusions: The demonstrated positive strong correlation between TT and DHEA in pre-pubertal male autistic children further substantiates the potential involvement of the adrenal cortex in the pathogenesis of autism. Further studies are needed to elucidate their role in the prediction and development of autism.

BDNF, proBDNF and IGF-1 serum levels in naïve and medicated subjects with autism

Brain-derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF-1) promote the development and maintenance of neural circuits. Alterations in these factors might contribute to autism spectrum disorder (ASD). We asked whether serum BDNF, proBDNF, and IGF-1 levels are altered in an ASD population compared to controls. We measured serum BDNF, proBDNF, and IGF-1 immunoreactive protein in boys and girls aged 5–15 years old with mild to moderate ASD and non-autistic controls by ELISA. IGF-1 was increased in ASD serum compared to controls and was correlated with age and with CARS scores. Serum BDNF levels did not differ between groups, however, proBDNF serum levels were decreased in subjects with ASD compared to non-autistic controls. Medicated, but not unmedicated, ASD subjects exhibited lower serum proBDNF levels compared to controls, while neither IGF-1 nor BDNF levels differed between treatment groups. These data support the involvement of proBDNF and IGF-1 in the pathogenesis and treatment of autism.

Progress in magnetic resonance imaging of autism model mice brain.

Autism spectrum disorder (ASD) is a neurodevelopmental disease characterized by social disorder and stereotypical behaviors with an increasing incidence. ASD patients are suffering from varying degrees of mental retardation and language development abnormalities. Magnetic resonance imaging (MRI) is a noninvasive imaging technology to detect brain structural and functional dysfunction in vivo, playing an important role in the early diagnosisbasic research of ASD. High-field, small-animal MRI in basic research of autism model mice has provided a new approach to research the pathogenesis, characteristics, and intervention efficacy in autism. This article reviews MRI studies of mouse models of autism over the past 20 years. Reduced gray matter, abnormal connections of brain networks, and abnormal development of white matter fibers have been demonstrated in these studies, which are present in different proportions in the various mouse models. This provides a more macroscopic view for subsequent research on autism model mice. This article is categorized under: Cognitive Biology > Genes and Environment Neuroscience > Computation Neuroscience > Genes, Molecules, and Cells Neuroscience > Development.

Multiple exposure to methylmercury aggravates DNA damage in the BTBR T + Itpr3 tf/J autistic mouse model: The role of DNA repair efficiency

Environmental and genetic factors have been recognized to play major roles in the pathogenesis of autism. Here we examined the BTBR T+Itpr3tf/J (BTBR) mice’s susceptibility, an autistic model, to the genotoxic effects and DNA repair dysregulation of methylmercury. Micronuclei formation and oxidative DNA damage were analyzed using the micronucleus/fluorescence in situ hybridization test and modified comet assay, respectively. The results showed higher centromeric-positive micronuclei and oxidative DNA damage in BTBR mice exposed to methylmercury than the unexposed mice, which indicates that mutagenesis aggravated in BTBR mice after methylmercury exposure. Lipid peroxides in BTBR mice were significantly elevated, with a decrease in reduced/oxidized glutathione ratio after methylmercury exposure, indicating an augmenting oxidant-antioxidant imbalance. The expression of several genes involved in DNA repair was markedly altered in BTBR mice after methylmercury exposure as evaluated via PCR array and RT-PCR analyses. Declining of the antioxidant defense and dysregulation in DNA repair process after methylmercury exposure may explain the aggravated genotoxic susceptibility of BTBR mice. Thus, autistic individuals exposed to methylmercury must be under regular medical follow-up through standard timetabled medical laboratory inquiry to allow for early recognition of any mutagenic changes. Additionally, strategies that elevate cellular antioxidants/DNA repair efficiency may counteract methylmercury-induced genotoxicity.

PI3K/AKT/mTOR signalling inhibitor chrysophanol ameliorates neurobehavioural and neurochemical defects in propionic acid-induced experimental model of autism in adult rats.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder marked by social and communication deficits as well as repetitive behaviour. Several studies have found that overactivation of the PI3K/AKT/mTOR signalling pathways during brain development plays a significant role in autism pathogenesis. Overexpression of the PI3K/AKT/mTOR signalling pathway causes neurological disorders by increasing cell death, neuroinflammation, and oxidative stress. Chrysophanol, also known as chrysophanic acid, is a naturally occurring chemical obtained from the plant Rheum palmatum. This study aimed to examine the neuroprotective effect of CPH on neurobehavioral, molecular, neurochemical, and gross pathological alterations in ICV-PPA induced experimental model of autism in adult rats. The effects of ICV-PPA on PI3K/AKT/mTOR downregulation in the brain were studied in autism-like rats. Furthermore, we investigated how CPH affected myelin basic protein (MBP) levels in rat brain homogenate and apoptotic biomarkers such as caspase-3, Bax, and Bcl-2 levels in rat brain homogenate and blood plasma samples. Rats were tested for behavioural abnormalities such as neuromuscular dysfunction using an actophotometer, motor coordination using a beam crossing task (BCT), depressive behaviour using a forced swim test (FST), cognitive deficiency, and memory consolidation using a Morris water maze (MWM) task. In PPA-treated rats, prolonged oral CPH administration from day 12 to day 44 of the experimental schedule reduces autistic-like symptoms. Furthermore, in rat brain homogenates, blood plasma, and CSF samples, cellular, molecular, and cell death markers, neuroinflammatory cytokines, neurotransmitter levels, and oxidative stress indicators were investigated. The recent findings imply that CPH also restores abnormal neurochemical levels and may prevent autism-like gross pathological alterations, such as demyelination volume, in the rat brain.

The "Primitive Brain Dysfunction" Theory of Autism: The Superior Colliculus Role.

A better understanding of the pathogenesis of autism will help clarify our conception of the complexity of normal brain development. The crucial deficit may lie in the postnatal changes that vision produces in the brainstem nuclei during early life. The superior colliculus is the primary brainstem visual center. Although difficult to examine in humans with present techniques, it is known to support behaviors essential for every vertebrate to survive, such as the ability to pay attention to relevant stimuli and to produce automatic motor responses based on sensory input. From birth to death, it acts as a brain sentinel that influences basic aspects of our behavior. It is the main brainstem hub that lies between the environment and the rest of the higher neural system, making continuous, implicit decisions about where to direct our attention. The conserved cortex-like organization of the superior colliculus in all vertebrates allows the early appearance of primitive emotionally-related behaviors essential for survival. It contains first-line specialized neurons enabling the detection and tracking of faces and movements from birth. During development, it also sends the appropriate impulses to help shape brain areas necessary for social-communicative abilities. These abilities require the analysis of numerous variables, such as the simultaneous evaluation of incoming information sustained by separate brain networks (visual, auditory and sensory-motor, social, emotional, etc.), and predictive capabilities which compare present events to previous experiences and possible responses. These critical aspects of decision-making allow us to evaluate the impact that our response or behavior may provoke in others. The purpose of this review is to show that several enigmas about the complexity of autism might be explained by disruptions of collicular and brainstem functions. The results of two separate lines of investigation: 1. the cognitive, etiologic, and pathogenic aspects of autism on one hand, and two. the functional anatomy of the colliculus on the other, are considered in order to bridge the gap between basic brain science and clinical studies and to promote future research in this unexplored area.

A common epigenetic mechanism across different cellular origins underlies systemic immune dysregulation in an idiopathic autism mouse model.

Immune dysregulation plays a key role in the pathogenesis of autism. Changes occurring at the systemic level, from brain inflammation to disturbed innate/adaptive immune in the periphery, are frequently observed in patients with autism; however, the intrinsic mechanisms behind them remain elusive. We hypothesize a common etiology may lie in progenitors of different types underlying widespread immune dysregulation. By single-cell RNA sequencing (sc-RNA seq), we trace the developmental origins of immune dysregulation in a mouse model of idiopathic autism. It is found that both in aorta-gonad-mesonephros (AGM) and yolk sac (YS) progenitors, the dysregulation of HDAC1-mediated epigenetic machinery alters definitive hematopoiesis during embryogenesis and downregulates the expression of the AP-1 complex for microglia development. Subsequently, these changes result in the dysregulation of the immune system, leading to gut dysbiosis and hyperactive microglia in the brain. We further confirm that dysregulated immune profiles are associated with specific microbiota composition, which may serve as a biomarker to identify autism of immune-dysregulated subtypes. Our findings elucidate a shared mechanism for the origin of immune dysregulation from the brain to the gut in autism and provide new insight to dissecting the heterogeneity of autism, as well as the therapeutic potential of targeting immune-dysregulated autism subtypes.

Characterization of cell-cell communication in autistic brains with single-cell transcriptomes

BackgroundAutism spectrum disorder is a neurodevelopmental disorder, affecting 1–2% of children. Studies have revealed genetic and cellular abnormalities in the brains of affected individuals, leading to both regional and distal cell communication deficits.MethodsRecent application of single-cell technologies, especially single-cell transcriptomics, has significantly expanded our understanding of brain cell heterogeneity and further demonstrated that multiple cell types and brain layers or regions are perturbed in autism. The underlying high-dimensional single-cell data provides opportunities for multilevel computational analysis that collectively can better deconvolute the molecular and cellular events altered in autism. Here, we apply advanced computation and pattern recognition approaches on single-cell RNA-seq data to infer and compare inter-cell-type signaling communications in autism brains and controls.ResultsOur results indicate that at a global level, there are cell-cell communication differences in autism in comparison with controls, largely involving neurons as both signaling senders and receivers, but glia also contribute to the communication disruption. Although the magnitude of changes is moderate, we find that excitatory and inhibitor neurons are involved in multiple intercellular signaling that exhibits increased strengths in autism, such as NRXN and CNTN signaling. Not all genes in the intercellular signaling pathways show differential expression, but genes in the affected pathways are enriched for axon guidance, synapse organization, neuron migration, and other critical cellular functions. Furthermore, those genes are highly connected to and enriched for genes previously associated with autism risks.ConclusionsOverall, our proof-of-principle computational study using single-cell data uncovers key intercellular signaling pathways that are potentially disrupted in the autism brains, suggesting that more studies examining cross-cell type effects can be valuable for understanding autism pathogenesis.

Immune Dysregulation in Autism Spectrum Disorder: What Do We Know about It?

Autism spectrum disorder (ASD) is a group of complex multifactorial neurodevelopmental disorders characterized by a wide and variable set of neuropsychiatric symptoms, including deficits in social communication, narrow and restricted interests, and repetitive behavior. The immune hypothesis is considered to be a major factor contributing to autism pathogenesis, as well as a way to explain the differences of the clinical phenotypes and comorbidities influencing disease course and severity. Evidence highlights a link between immune dysfunction and behavioral traits in autism from several types of evidence found in both cerebrospinal fluid and peripheral blood and their utility to identify autistic subgroups with specific immunophenotypes; underlying behavioral symptoms are also shown. This review summarizes current insights into immune dysfunction in ASD, with particular reference to the impact of immunological factors related to the maternal influence of autism development; comorbidities influencing autism disease course and severity; and others factors with particular relevance, including obesity. Finally, we described main elements of similarities between immunopathology overlapping neurodevelopmental and neurodegenerative disorders, taking as examples autism and Parkinson Disease, respectively.

Altered Expression of Brain-specific Autism-Associated miRNAs in the Han Chinese Population.

Autism is a complex neurodevelopmental disorder. However, its etiology is still unknown. MicroRNAs (miRNAs) are key post-transcriptional regulators. They play an important role in neurodevelopment and brain functions and may be involved in the pathogenesis of autism. Previous studies indicated altered expression of miRNAs in patients with autism. However, the findings were not consistent, and further explorations were needed. This study aimed to investigate whether miRNAs were dysregulated in autism. We examined the expression of 30 brain-specific autism-associated miRNAs in 110 patients with autism and 113 controls in the Han Chinese population using quantitative reverse transcription–polymerase chain reaction. The results demonstrated that 10 miRNAs (hsa-miR-191-5p, hsa-miR-151a-3p, hsa-miR-139-5p, hsa-miR-181a-5p, hsa-miR-432-5p, hsa-miR-181b-5p, hsa-miR-195-5p, hsa-miR-328-3p, hsa-miR-106a-5p, and hsa-miR-484) were significantly differentially expressed (false discovery rate <0.05). All of them were up-regulated in patients with autism compared with controls. The targets of these miRNAs were enriched for genes and pathways related to neurodevelopment, brain functions and autism. These findings suggested the participation of these 10 miRNAs in the pathogenesis of autism in the Han Chinese population.

The Gut-Brain-Immune Axis in Autism Spectrum Disorders: A State-of-Art Report.

The interest elicited by the large microbial population colonizing the human gut has ancient origins and has gone through a long evolution during history. However, it is only in the last decades that the introduction of high-throughput technologies has allowed to broaden this research field and to disentangle the numerous implications that gut microbiota has in health and disease. This comprehensive ecosystem, constituted mainly by bacteria but also by fungi, parasites, and viruses, is proven to be involved in several physiological and pathological processes that transcend the intestinal homeostasis and are deeply intertwined with apparently unrelated body systems, such as the immune and the nervous ones. In this regard, a novel speculation is the relationship between the intestinal microbial flora and the pathogenesis of some neurological and neurodevelopmental disorders, including the clinical entities defined under the umbrella term of autism spectrum disorders. The bidirectional interplay has led researchers to coin the term gut-brain-immune system axis, subverting the theory of the brain as an immune-privileged site and underscoring the importance of this reciprocal influence already from fetal life and especially during the pre- and post-natal neurodevelopmental process. This revolutionary theory has also unveiled the possibility to modify the gut microbiota as a way to treat and even to prevent different kinds of pathologies. In this sense, some attempts have been made, ranging from probiotic administration to fecal microbiota transplantation, with promising results that need further elaboration. This state-of-art report will describe the main aspects regarding the human gut microbiome and its specific role in the pathogenesis of autism and its related disorders, with a final discussion on the therapeutic and preventive strategies aiming at creating a healthy intestinal microbial environment, as well as their safety and ethical implications.

Guggulsterone Mediated JAK/STAT and PPAR-Gamma Modulation Prevents Neurobehavioral and Neurochemical Abnormalities in Propionic Acid-Induced Experimental Model of Autism.

Autism spectrum disorder is a neurodevelopmental disorder marked by repetitive behaviour, challenges in verbal and non-verbal communication, poor socio-emotional health, and cognitive impairment. An increased level of signal transducer and activator of transcription 3 (STAT3) and a decreased level of peroxisome proliferator-activated receptor (PPAR) gamma have been linked to autism pathogenesis. Guggulsterone (GST) has a neuroprotective effect on autistic conditions by modulating these signalling pathways. Consequently, the primary objective of this study was to examine potential neuroprotective properties of GST by modulating JAK/STAT and PPAR-gamma levels in intracerebroventricular propionic acid (ICV PPA) induced experimental model of autism in adult rats. In this study, the first 11 days of ICV-PPA injections in rats resulted in autism-like behavioural, neurochemical, morphological, and histopathological changes. The above modifications were also observed in various biological samples, including brain homogenate, CSF, and blood plasma. GST was also observed to improve autism-like behavioural impairments in autistic rats treated with PPA, including locomotion, neuromuscular coordination, depression-like behaviour, spatial memory, cognition, and body weight. Prolonged GST treatment also restored neurochemical deficits in a dose-dependent manner. Chronic PPA administration increased STAT3 and decreased PPAR gamma in autistic rat brain, CSF, and blood plasma samples, which were reversed by GST. GST also restored the gross and histopathological alterations in PPA-treated rat brains. Our results indicate the neuroprotective effects of GST in preventing autism-related behavioural and neurochemical alterations.

Oxidative DNA Damage of Peripheral Blood Cells and Blood Plasma Сell-Free DNA as an Indicator of the Oxidative Stress Level in Children with Autism Spectrum Disorders and Schizophrenia

Background: pathogen heterogeneity and complexity are the main obstacles for schizophrenia and autism spectrum disorders (ASD) differential diagnosis in children. The role of oxidative stress in the molecular mechanisms of schizophrenia and autism pathogenesis is beyond doubt. Free radicals that accumulate during stress can cause oxidative modifications and the formation of breaks in the сell-free DNA (cfDNA) and nuclear DNA of blood cells. To date, it has been proven that 8-hydroxy-2’- deoxyguanosine (8-OHdG) can be considered as an oxidative stress biomarker. However, it is still unclear how pronounced the genotoxic consequences of oxidative stress are in ASD of varying severity and in childhood onset schizophrenia (COS). Objective: to study the relationship between the oxidative DNA damage level in peripheral blood cells and the circulating cell-free DNA characteristics with the severity of COS and the course of ASD in children. Patients and methods: blood samples of 96 patients with childhood autism (CA — F84.0 according to ICD-10), atypical autism (AA — F84.1 according to ICD-10) and with childhood onset schizophrenia (COS — F20.8 according to ICD-10) were obtained from the Child Psychiatry Department of the Mental health research center. Blood samples of the control group (34 people) — from the collection of samples of the Research Centre for medical Genetics. The selection of patients was carried out using the clinical and psychopathological method. Cell-free DNA was isolated by extraction with organic solvents. The concentration of cfDNA was determined fluorimetrically. The level of 8-OHdG in cell-free DNA was determined by binding of the corresponding antibodies on membrane filters, endonuclease activity was determined by radial diffusion in a gel. G0-peripheral blood lymphocytes were isolated by gradient centrifugation. The level of 8-OHdG and the level of the phosphorylated form of histone H2AX (yH2AX) in G0-peripheral blood lymphocytes were analyzed in fixed cells by flow cytofluorometry using appropriate antibodies. Statistical processing was carried out using Microsoft Office Excel, Statistica 6.0, StatGraph. Results and conclusions: oxidative stress has different severity in ASD, occurring in severe form (AA) and mild/moderate form (CA). In CA, the level of oxidative damage to the DNA of lymphocytes tends to increase, but does not reach statistically significant level; the level of oxidative damage to cfDNA does not differ from the control. In AA and, to an even stronger extent, in COS, the level of oxidative damage to the DNA of cells and cfDNA is significantly increased, which indicates the development of systemic oxidative stress, which is not compensated by the body’s antioxidant system. The level of 8-OHdG in the composition of the cfDNA and DNA of the nuclei of peripheral blood cells can be a marker of oxidative stress, which is important not only for diagnosing the severity of the pathological process, but also for treatment regimens development for COS and ASD in children.

AN OBSERVATIONAL STUDY TO ASSESS THE PARENTAL DOSHA PRAKRITI OF AUTISTIC CHILDREN

Prakriti refers to the genetically determined physical and mental constitution of an individual. Autism is a lifelong disability identified by impaired communication, social interaction and repetitive behaviours. The genetic, envi- ronmental and immunological factors play an important role in generating autism. Genetic factors are more pre- dominant in autism pathogenesis than the environmental factors that would modulate the phenotype. Until now, no interventions have proven widely effective in providing complete relief to autism. Therefore, the prevention of autism needs supreme attention. To a greater extent, prakriti of an individual can determine proneness to particu- lar diseases. To assess the prakriti of both parents of 30 diagnosed cases of autistic children attending the OPD and IPD of Govt. Ayurveda College, Kannur were randomly selected. They are subjected to detailed history taking based on specially prepared proforma and assessments were recorded. Their prakriti assessment was done using a validated computer-assisted questionnaire software Ayusoft developed by C-DAC Pune. The data was statistically analysed. In this study, Vata pitta prakriti was significantly seen in mothers of autistic children. Keywords: Prakriti, Autism

The Role of Maternal Immune Activation in the Pathogenesis of Autism: A Review of the Evidence, Proposed Mechanisms and Implications for Treatment.

Autism spectrum disorder (ASD) is a neurodevelopmental disease that is characterized by a deficit in social interactions and communication, as well as repetitive and restrictive behaviors. Increasing lines of evidence suggest an important role for immune dysregulation and/or inflammation in the development of ASD. Recently, a relationship between inflammation, oxidative stress, and mitochondrial dysfunction has been reported in the brain tissue of individuals with ASD. Some recent studies have also reported oxidative stress and mitochondrial abnormalities in animal models of maternal immune activation (MIA). This review is focused on the hypothesis that MIA induces microglial activation, oxidative stress, and mitochondrial dysfunction, a deleterious trio in the brain that can lead to neuroinflammation and neurodevelopmental pathologies in offspring. Infection during pregnancy activates the mother’s immune system to release proinflammatory cytokines, such as IL-6, TNF-α, and others. Furthermore, these cytokines can directly cross the placenta and enter the fetal circulation, or activate resident immune cells, resulting in an increased production of proinflammatory cytokines, including IL-6. Proinflammatory cytokines that cross the blood–brain barrier (BBB) may initiate a neuroinflammation cascade, starting with the activation of the microglia. Inflammatory processes induce oxidative stress and mitochondrial dysfunction that, in turn, may exacerbate oxidative stress in a self-perpetuating vicious cycle that can lead to downstream abnormalities in brain development and behavior.

A systematic review of common genetic variation and biological pathways in autism spectrum disorder

BackgroundAutism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by persistent deficits in social communication and interaction. Common genetic variation appears to play a key role in the development of this condition. In this systematic review, we describe the relationship between genetic variations and autism. We created a gene dataset of the genes involved in the pathogenesis of autism and performed an over-representation analysis to evaluate the biological functions and molecular pathways that may explain the associations between these variants and the development of ASD.Results177 studies and a gene set composed of 139 were included in this qualitative systematic review. Enriched pathways in the over-representation analysis using the KEGG pathway database were mostly associated with neurotransmitter receptors and their subunits. Major over-represented biological processes were social behavior, vocalization behavior, learning and memory. The enriched cellular component of the proteins encoded by the genes identified in this systematic review were the postsynaptic membrane and the cell junction.ConclusionsAmong the biological processes that were examined, genes involved in synaptic integrity, neurotransmitter metabolism, and cell adhesion molecules were significantly involved in the development of autism.