Repetitive Stereotyped Behaviors Research Articles

Autism risk gene Cul3 alters neuronal morphology via caspase-3 activity in mouse hippocampal neurons.

Autism Spectrum Disorders (ASDs) are neurodevelopmental disorders (NDDs) in which children display differences in social interaction/communication and repetitive stereotyped behaviors along with variable associated features. Cul3, a gene linked to ASD, encodes CUL3 (CULLIN-3), a protein that serves as a key component of a ubiquitin ligase complex with unclear function in neurons. Cul3 homozygous deletion in mice is embryonic lethal; thus, we examine the role of Cul3 deletion in early synapse development and neuronal morphology in hippocampal primary neuronal cultures. Homozygous deletion of Cul3 significantly decreased dendritic complexity and dendritic length, as well as axon formation. Synaptic spine density significantly increased, mainly in thin and stubby spines along with decreased average spine volume in Cul3 knockouts. Both heterozygous and homozygous knockout of Cul3 caused significant reductions in the density and colocalization of gephyrin/vGAT puncta, providing evidence of decreased inhibitory synapse number, while excitatory synaptic puncta vGulT1/PSD95 density remained unchanged. Based on previous studies implicating elevated caspase-3 after Cul3 deletion, we demonstrated increased caspase-3 in our neuronal cultures and decreased neuronal cell viability. We then examined the efficacy of the caspase-3 inhibitor Z-DEVD-FMK to rescue the decrease in neuronal cell viability, demonstrating reversal of the cell viability phenotype with caspase-3 inhibition. Studies have also implicated caspase-3 in neuronal morphological changes. We found that caspase-3 inhibition largely reversed the dendrite, axon, and spine morphological changes along with the inhibitory synaptic puncta changes. Overall, these data provide additional evidence that Cul3 regulates the formation or maintenance of cell morphology, GABAergic synaptic puncta, and neuronal viability in developing hippocampal neurons in culture.

Analysis of Different Treatment Methods for Autism

Autism, the full name of autism spectrum disorder, is a type of inborn, congenital, or onset in infancy, characterized by social communication difficulties, narrow interests, repetitive stereotyped behaviors, and sensory perception. In recent decades, the incidence of autism has been increasing worldwide. It is estimated that the average prevalence of autism worldwide is about 1%. Therefore, there is no doubt that autism has become a public health issue that has attracted great attention and attention from societies and governments around the world. It is also one of the key topics in neuro-medical research today, although many researchers have conducted corresponding clinical experiments on treatments for autism. However, there are still some unresolved problems in the treatment of autism in Chinese medicine. As a result, this article uses literature review and survey research methods, mainly studies and summarizes traditional Chinese and Western medicine in the treatment of autism and compares the shortcomings of traditional Chinese medicine in the treatment of patients with autism. And the treatment and popularization of autism still need to continue to be researched and promoted.

Personalized repetitive transcranial magnetic stimulation guided by the spectral electroencephalogram may enhance and democratize therapy for autism spectrum disorder

Autism spectrum disorder (ASD) is a genetically heterogeneous group of neurodevelopmental disorders that affect 1 in 36 children (CDC data) and have recognizable core deficits in common, including repetitive stereotyped behaviors and difficulties in social interaction and communication. Pharmacological interventions moderate some ASD comorbidities, but do not alleviate core deficits and have significant side effects. While many behavioral therapies are inadequate, a very intensive form called applied behavioral analysis (ABA) is demonstrably effective. ABA is based on graded progression and immediate feedback. ABA has raised concerns over its intensive nature and has triggered unease about being too harsh. One solution may derive from a widespread hypothesis of ASD pathogenesis, which posits that the brain in ASD is overexcited, i.e., excitation dominates over inhibition, and electroencephalographic (EEG) alpha band oscillatory activity is altered, which degrades sensory input and task management. This may also disrupt the brain mesolimbic dopaminergic reward cascade causing social interactions to be unrewarding, leading to deleterious social behavior and poor communication. We hypothesize that a comprehensive, personalized form of spectral EEG guided repetitive transcranial magnetic stimulation that we term PrTMS, can normalize alpha EEG oscillations, E/I balance, and dopaminergic reward signaling, to facilitate improved psychosocial behavior. The goal is for PrTMS to synergize with behavioral interventions, so that ABA for example, could be less intensive. This may hold the promise of making self-determination more readily attainable for ASD persons, and could also democratize ASD therapy by rendering it more affordable.

Between Dysbiosis, Maternal Immune Activation and Autism: Is There a Common Pathway?

Autism spectrum disorder (ASD) is a neuropsychiatric condition characterized by impaired social interactions and repetitive stereotyped behaviors. Growing evidence highlights an important role of the gut-brain-microbiome axis in the pathogenesis of ASD. Research indicates an abnormal composition of the gut microbiome and the potential involvement of bacterial molecules in neuroinflammation and brain development disruptions. Concurrently, attention is directed towards the role of short-chain fatty acids (SCFAs) and impaired intestinal tightness. This comprehensive review emphasizes the potential impact of maternal gut microbiota changes on the development of autism in children, especially considering maternal immune activation (MIA). The following paper evaluates the impact of the birth route on the colonization of the child with bacteria in the first weeks of life. Furthermore, it explores the role of pro-inflammatory cytokines, such as IL-6 and IL-17a and mother's obesity as potentially environmental factors of ASD. The purpose of this review is to advance our understanding of ASD pathogenesis, while also searching for the positive implications of the latest therapies, such as probiotics, prebiotics or fecal microbiota transplantation, targeting the gut microbiota and reducing inflammation. This review aims to provide valuable insights that could instruct future studies and treatments for individuals affected by ASD.

Nomo1 deficiency causes autism-like behavior in zebrafish.

Patients with neuropsychiatric disorders often exhibit a combination of clinical symptoms such as autism, epilepsy, or schizophrenia, complicating diagnosis and development of therapeutic strategies. Functional studies of novel genes associated with co-morbidities can provide clues to understand the pathogenic mechanisms and interventions. NOMO1 is one of the candidate genes located at 16p13.11, a hotspot of neuropsychiatric diseases. Here, we generate nomo1-/- zebrafish to get further insight into the function of NOMO1. Nomo1 mutants show abnormal brain and neuronal development and activation of apoptosis and inflammation-related pathways in the brain. Adult Nomo1-deficient zebrafish exhibit multiple neuropsychiatric behaviors such as hyperactive locomotor activity, social deficits, and repetitive stereotypic behaviors. The Habenular nucleus and the pineal gland in the telencephalon are affected, and the melatonin level of nomo1-/- is reduced. Melatonin treatment restores locomotor activity, reduces repetitive stereotypic behaviors, and rescues the noninfectious brain inflammatory responses caused by nomo1 deficiency. These results suggest melatonin supplementation as a potential therapeutic regimen for neuropsychiatric disorders caused by NOMO1 deficiency.

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.

Replication of previous autism-GWAS hits suggests the association between NAA1, SORCS3, and GSDME and autism in the Han Chinese population

BackgroundAutism is a severe neurodevelopmental disorder characterized by social interaction deficits, impairments in communication, and restricted and repetitive stereotyped behavior and activities. Family and twin studies suggested an essential role of genetic factors in the etiology of autism spectrum disorder (ASD). Also, other studies found SORCS3 and GSDME (DFNA5) might be involved in brain development and susceptible to ASD. MethodsIn this study, 17 genome-wide significant SNPs reported in previous ASD genome-wide association studies (GWAS) and 7 SNPs in strong linkage disequilibrium with known ASD GWAS hits were selected to investigate the association between these SNPs and autism in the Han Chinese population. Then, 10 tagSNPs in SORCS3 and 11 tagSNPs in GSDME were selected to analyze the association between these SNPs and autism. The selected 24 SNPs and tagSNPs were genotyped using the Agena MassARRAY SNP genotyping assay in 757 Han Chinese autism trios. ResultsRs1484144 in NAA11 was significantly associated with autism; significance remained after the Bonferroni correction (P < 0.0022). Also, rs79879286, rs12154597, and rs12540919 near GSDME, as well as rs9787523 and rs3750261 in SORCS3, were nominally associated with autism. ConclusionOur study suggests that rs1484144 in NAA11 is a significant SNP for autism in the Han Chinese population, while SORCS3 and GSDME might be the susceptibility genes for autism in this population.

Oxytocin treatment for core symptoms in children with autism spectrum disorder: a systematic review and meta-analysis.

The purpose of this article is to examine the efficacy of oxytocin in treating core symptoms of autism spectrum disorder (ASD) with children. A systematic literature search was conducted to identify randomized controlled trials (RCTs) of oxytocin for the treatment of core symptoms in children with ASD. The search included studies published between January 1, 1999 and March 15, 2023, that were randomized, single or double-blinded, and included a placebo control group. Standard screening rules were applied to select relevant studies, resulting in the inclusion of five RCTs involving 486 children with ASD. Ultimately, a total of five RCTs, involving 486 children with ASD, were included in the review using standard screening rules.One of the included studies demonstrated a statistically significant improvement in Social Responsiveness Scale (SRS) and Repetitive Behavior Scale-Revised (RBS) scores when children with ASD were treated with oxytocin (24 IU/2 days for 6 weeks). The improvement in core symptoms persisted at the 6-month follow-up. The meta-analysis findings suggested that oxytocin might have a moderate effect in improving the core symptom of narrow interests and repetitive stereotyped behaviors in children with ASD. While the therapeutic value of oxytocin in treating core symptoms of ASD in children is not fully established, the results of this meta-analysis indicate a potential moderate effect. However, further studies with larger sample sizes and more robust RCTs are needed to directly demonstrate the efficacy of oxytocin. Future research should also focus on effect size and outcome evaluation accuracy while minimizing bias in RCT experiments.

Effect of simvastatin on brain-derived neurotrophic factor (BDNF)/TrkB pathway in hippocampus of autism rat model

Purpose: To study the effect of simvastatin on behavioral performance in a rat model of autism, and its effect on hippocampal brain-derived BDNF-TrkB pathway.&#x0D; Methods: Twelve rats with valproic acid (VPA)-induced autism were randomly divided into model group and simvastatin group, while six healthy rats served as normal control group. Rats in the simvastatin group received the drug (5 mg/kg) via i.p. route, while rats in model group and normal control group were injected with equivalent volume of normal saline in place of simvastatin. Capacity for interaction and repetitive stereotyped behavior, as well as results of Morris water maze test were determined for each group. The expressions of BDNF-TrkB proteins were assayed with immunoblotting.&#x0D; Results: The frequencies of sniffing normal saline, alcohol and rat urine were significantly higher in model and simvastatin rats than in normal rats, but they were significantly lower in simvastatin-treated rats than in model rats (p &lt; 0.05). There was higher duration of turning, jumping and grooming in the model group and simvastatin group than in the normal rats, but the duration was significantly reduced in simvastatin rats, relative to model rats. Escape latency times was significantly longer in model and simvastatin rats than in controls, but number of target quadrant crossings was significantly reduced. However, escape latency time was lower in simvastatin rats than in model rats, but number of target quadrant crossings was significantly higher. The model and simvastatin rats had down-regulated levels of BDNF and TrkB protein, relative to control rats, but there were markedly higher levels of these proteins in simvastatin-treated rats than in model rats.&#x0D; Conclusion: Simvastatin improves the behavioral performance of autistic rats by regulating BDNF/TrkB signal axis. This finding may be useful in the development of new drugs for treating autism.

A Review of Sand-play in Preschool Integrated Education for Autistic Children

With the deepening of peoples understanding of autism, more and more attention has been paid to the group of autistic children. Sandplay therapy as a treatment for autism is not only easy to operate, easy to implement, has a deep theoretical basis as support, but also deeply loved by children, at the same time, it has also been widely recognized in the world, which has some effect in alleviating autistic children's social interaction barriers, language barriers, and repetitive stereotypic behaviors. And since the concept of integrated education was put forward, more and more autistic children have started to study in ordinary schools. As an inexorable trend in the field of special education, the aim is to place children with special needs in regular classes to maximize their potential of children with special needs and enable them to grow up together with ordinary children. In the tide of integrated education, schools will become the best place for autistic children to learn and play sandplay. Based on the analysis of the effects of sandplay on autistic children's interpersonal communication disorder, speech disorder, and repetitive stereotypic behavior, this paper puts forward the basic principles and practical conditions of applying sandplay to preschool integrated education and points out the limitations and future research directions of sandplay in the practice of integrated education.

Exploring the heterogeneity of brain structure in autism spectrum disorder based on individual structural covariance network.

Autism spectrum disorder (ASD) is characterized by highly structural heterogeneity. However, most previous studies analyzed between-group differences through a structural covariance network constructed based on the ASD group level, ignoring the effect of between-individual differences. We constructed the gray matter volume-based individual differential structural covariance network (IDSCN) using T1-weighted images of 207 children (ASD/healthy controls: 105/102). We analyzed structural heterogeneity of ASD and differences among ASD subtypes obtained by a K-means clustering analysis based on evidently different covariance edges relative to healthy controls. The relationship between the distortion coefficients (DCs) calculated at the whole-brain, intra- and interhemispheric levels and the clinical symptoms of ASD subtypes was then examined. Compared with the control group, ASD showed significantly altered structural covariance edges mainly involved in the frontal and subcortical regions. Given the IDSCN of ASD, we obtained 2 subtypes, and the positive DCs of the 2 ASD subtypes were significantly different. Intra- and interhemispheric positive and negative DCs can predict the severity of repetitive stereotyped behaviors in ASD subtypes 1 and 2, respectively. These findings highlight the crucial role of frontal and subcortical regions in the heterogeneity of ASD and the necessity of studying ASD from the perspective of individual differences.

MTOR Signaling Disruption and Its Association with the Development of Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by impairments in social interaction and communication along with repetitive stereotypic behaviors. Currently, there are no specific biomarkers for diagnostic screening or treatments available for autistic patients. Numerous genetic disorders are associated with high prevalence of ASD, including tuberous sclerosis complex, phosphatase and tensin homolog, and fragile X syndrome. Preclinical investigations in animal models of these diseases have revealed irregularities in the PI3K/Akt/mTOR signaling pathway as well as ASD-related behavioral defects. Reversal of the downstream molecular irregularities, associated with mTOR hyperactivation, improved the behavioral deficits observed in the preclinical investigations. Plant bioactive molecules have shown beneficial pre-clinical evidence in ASD treatment by modulating the PI3K/Akt/mTOR pathway. In this review, we summarize the involvement of the PI3K/Akt/mTOR pathway as well as the genetic alterations of the pathway components and its critical impact on the development of the autism spectrum disorder. Mutations in negative regulators of mTORC1, such as TSC1, TSC2, and PTEN, result in ASD-like phenotypes through the disruption of the mTORC1-mediated signaling. We further discuss the various naturally occurring phytoconstituents that have been identified to be bioactive and modulate the pathway to prevent its disruption and contribute to beneficial therapeutic effects in ASD.

Diffusion tensor imaging analysis of the corpus callosum in children with high-risk autism spectrum disorder.

Autism spectrum disorder (ASD) is a severe neurodevelopmental disorder that begins in early infancy and childhood and is characterized by impaired social communication and repetitive stereotyped behaviors. The purpose of this study was to examine the development of the corpus callosum and its relationship to neurobehavior in young children with high-risk (HR) ASD using magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). Twenty-one children with HR-ASD who visited Anhui Children's Hospital between January 2020 and December 2021 were selected as the study group, while 19 matched children with normal development during the same time were adopted as the control group. Cranial MRI+DTI were performed for all of the enrolled children and fractional anisotropy (FA) measurements were taken in each region of the corpus callosum. The FA values in all regions of the corpus callosum were higher in the study group than in the control group (0.417 ± 0.016 vs. 0.412 ± 0.02 in the corpus callosum knee, 0.439 ± 0.018 vs. 0.431 ± 0.023 in the corpus callosum body, and 0.446 ± 0.017 vs. 0.434 ± 0.019 in the splenium of corpus callosum [SCC]), where the difference in the FA in the SCC was statistically significant between the two groups (P< 0.05). There was a positive correlation between the FA in the corpus callosum knee and speech scores in the neuropsychological development of the study group (P< 0.05). There was a premature development tendency for corpus callosum myelination in young children with HR-ASD, and the developmental tendency was visible in the SCC. There was also a positive relationship between corpus callosum knee development and language function.

MiRNAs as biomarkers of autism spectrum disorder: a systematic review and meta-analysis.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with complex clinical manifestations that arise between 18 and 36months of age. Social interaction deficiencies, a restricted range of interests, and repetitive stereotyped behaviors are characteristics which are sometimes difficult to detect early. Several studies show that microRNAs (miRs/miRNAs) are strongly implicated in the development of the disorder and affect the expression of genes related to different neurological pathways involved in ASD. The present systematic review and meta-analysis addresses the current status of miRNA studies in different body fluids and the most frequently dysregulated miRNAs in patients with ASD. We used a combined approach to summarize miRNA fold changes in different studies using the mean values. In addition, we summarized p values for differential miRNA expression using the Fisher method. Our literature search yielded a total of 133 relevant articles, 27 of which were selected for qualitative analysis based on the inclusion and exclusion criteria, and 16 studies evaluating miRNAs whose data were completely reported were ultimately included in the meta-analysis. The most frequently dysregulated miRNAs across the analyzed studies were miR-451a, miR-144-3p, miR-23b, miR-106b, miR150-5p, miR320a, miR92a-2-5p, and miR486-3p. Among the most dysregulated miRNAs in individuals with ASD, miR-451a is the most relevant to clinical practice and is associated with impaired social interaction. Other miRNAs, including miR19a-3p, miR-494, miR-142-3p, miR-3687, and miR-27a-3p, are differentially expressed in various tissues and body fluids of patients with ASD. Therefore, all these miRNAs can be considered candidates for ASD biomarkers. Saliva may be the optimal biological fluid for miRNA measurements, because it is easy to collect from children compared to other biological fluids.

A dopaminergic reward prediction error signal shapes maternal behavior in mice

How social contact is perceived as rewarding and subsequently modifies interactions is unclear. Dopamine (DA) from the ventral tegmental area (VTA) regulates sociality, but the ongoing, unstructured nature of free behavior makes it difficult to ascertain how. Here, we tracked the emergence of a repetitive stereotyped parental retrieval behavior and conclude that VTA DA neurons incrementally refine it by reinforcement learning (RL). Trial-by-trial performance was correlated with the history of DA neuron activity, but DA signals were inconsistent with VTA directly influencing the current trial. We manipulated the subject's expectation of imminent pup contact and show that DA signals convey reward prediction error, a fundamental component of RL. Finally, closed-loop optogenetic inactivation of DA neurons at the onset of pup contact dramatically slowed emergence of parental care. We conclude that this component of maternal behavior is shaped by an RL mechanism in which social contact itself is the primary reward.

Autism spectrum disorders in boys at a major UK hemophilia center: prevalence and risk factors

BackgroundAutism spectrum disorders (ASDs) are diagnosed by social communication difficulties strong, narrow interests, and repetitive stereotyped behavior. An apparently-elevated prevalence of ASD at a major UK hemophilia center warranted investigation. ObjectivesTo screen boys with hemophilia for difficulties in social communication and executive function and identify the prevalence and risk factors for ASD. MethodsParents of boys with hemophilia aged 5 to 16 years completed the Social Communication Questionnaire, Children’s Communication Checklist, and the Behavior Rating Inventory of executive function. Prevalence and potential risk factors for ASD were evaluated. Boys with an existing diagnosis of ASD did not complete questionnaires, but were included in the prevalence analysis. ResultsNegative scores on all 3 questionnaires were observed for 60 of 79 boys. Positive scores on 1, 2, and 3 questionnaires were seen in 12 of 79, 3 of 79, and 4 of 79 boys, respectively. In addition to the 11 of 214 boys with a prior ASD diagnosis, 3 further boys were diagnosed with ASD, yielding a prevalence of 14 (6.5%) of 214, greater than that of boys in the UK general population. Premature birth was linked to having ASD, but did not fully explain the increased prevalence with more boys born <37 weeks scoring positively on the Social Communications Questionnaire and Children’s Communication Checklist compared with those born at term. ConclusionThis study identified an increased prevalence of ASD at 1 UK hemophilia center. Prematurity was identified as a risk factor but did not fully explain the higher prevalence of ASD. Further investigation in the wider national/global hemophilia communities is warranted to determine whether this is an isolated finding.

Downregulation of DDIT4 ameliorates abnormal behaviors in autism by inhibiting ferroptosis via the PI3K/Akt pathway

Autism spectrum disorder (ASD) is a complex disease with unclear etiology. Studies have shown that ferroptosis is also related to ASD progression, but the specific mechanism is still unclear. Valproic acid (VPA) induced neuronal ferroptosis in vitro. Mechanistic studies showed that both VPA and ferroptosis inducers promoted the expression of DDIT4 in neurons, thereby inhibiting the activation of the PI3K/Akt pathway. DDIT4 increased the accumulation of ROS, MDA and Fe2+, inhibited neuronal viability and downregulated GPX4 expression by inactivating the PI3K/Akt pathway. Ferroptosis inhibitors reversed the anti-survival effect of DDIT4, indicating that DDIT4 enhances ferroptosis through the PI3K/Akt pathway, thereby inhibiting neuronal viability. Further in vivo experiments found that autistic mice had high levels of ROS, MDA and Fe2+, increased DDIT4 expression, and downregulated expression levels of GPX4, p-PI3K and p-Akt; after downregulation of DDIT4 expression, the accumulation of ROS, MDA and Fe2+ was significantly reduced, while the expression levels of GPX4, p-PI3K and p-Akt were upregulated, indicating that DDIT4 knockdown reduces ferroptosis in autistic mice. In addition, DDIT4 downregulation, PI3K/Akt pathway activation, and ferroptosis inhibitors all improved social behavior deficits, repetitive stereotyped and compulsive behaviors, anxiety and exploratory behaviors in autistic mice, but PI3K/Akt pathway inhibitors significantly blocked the rescue of abnormal behaviors by DDIT4 downregulation in autistic mice. Therefore, downregulation of DDIT4 expression ameliorates abnormal behaviors in autism by inhibiting ferroptosis via the PI3K/Akt pathway, indicating that DDIT4, the PI3K/Akt pathway and ferroptosis have key roles in autism.

Midbrain dopamine neurons arbiter OCD-like behavior

The neurobiological understanding of obsessive-compulsive disorder (OCD) includes dysregulated frontostriatal circuitry and altered monoamine transmission. Repetitive stereotyped behavior (e.g., grooming), a featured symptom in OCD, has been proposed to be associated with perturbed dopamine (DA) signaling. However, the precise brain circuits participating in DA's control over this behavioral phenotype remain elusive. Here, we identified that DA neurons in substantia nigra pars compacta (SNc) orchestrate ventromedial striatum (VMS) microcircuits as well as lateral orbitofrontal cortex (lOFC) during self-grooming behavior. SNc-VMS and SNc-lOFC dopaminergic projections modulate grooming behaviors and striatal microcircuit function differentially. Specifically, the activity of the SNc-VMS pathway promotes grooming via D1 receptors, whereas the activity of the SNc-lOFC pathway suppresses grooming via D2 receptors. SNc DA neuron activity thus controls the OCD-like behaviors via both striatal and cortical projections as dual gating. These results support both pharmacological and brain-stimulation treatments for OCD.

Autism-like behaviors regulated by the serotonin receptor 5-HT2B in the dorsal fan-shaped body neurons of Drosophila melanogaster

BackgroundAutism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction and repetitive stereotyped behaviors. Previous studies have reported an association of serotonin or 5-hydroxytryptamine (5-HT) with ASD, but the specific receptors and neurons by which serotonin modulates autistic behaviors have not been fully elucidated.MethodsRNAi-mediated knockdown was done to destroy the function of tryptophan hydroxylase (Trh) and all the five serotonin receptors. Given that ubiquitous knockdown of 5-HT2B showed significant defects in social behaviors, we applied the CRISPR/Cas9 system to knock out the 5-HT2B receptor gene. Social space assays and grooming assays were the major methods used to understand the role of serotonin and related specific receptors in autism-like behaviors of Drosophila melanogaster.ResultsA close relationship was identified between serotonin and autism-like behaviors reflected by increased social space distance and high-frequency repetitive behavior in Drosophila. We further utilized the binary expression system to knock down all the five 5-HT receptors, and observed the 5-HT2B receptor as the main receptor responsible for the normal social space and repetitive behavior in Drosophila for the specific serotonin receptors underlying the regulation of these two behaviors. Our data also showed that neurons in the dorsal fan-shaped body (dFB), which expressed 5-HT2B, were functionally essential for the social behaviors of Drosophila.ConclusionsCollectively, our data suggest that serotonin levels and the 5-HT2B receptor are closely related to the social interaction and repetitive behavior of Drosophila. Of all the 5 serotonin receptors, 5-HT2B receptor in dFB neurons is mainly responsible for serotonin-mediated regulation of autism-like behaviors.

Influencing factors and intervention therapy of the Autism Spectrum Disorder (ASD)

Autism spectrum disorder (ASD) is a kind of the disorder which is characterized by continuous social interaction and communication disorders, narrow interests and repetitive stereotyped behaviors are the main core symptoms of neurodevelopmental disorders. At the same time, the incidence of the disease increases rapidly and is extremely harmful, which brings huge economic burden to families and society. Therefore, early identification and early intervention are urgently needed. At present, the pathogenesis of ASD is not clear, and there is no perfect diagnostic tools and methods. So far, scholars are still exploring the etiology and pathogenesis of ASD. In the past, researchers have paid attention to the study of twins and found that the prevalence of monozygotic twins is higher than that of dizygotic twins, so as to try to explain the ASD from a genetic perspective.Academic circles generally believe that ASD is caused by the joint action of genetics and environment. In order to find the objective indicators of early recognition of ASD individuals, researchers have actively carried out research on ASD infants, such as twins, the overall processing of isolated faces,event-related potentials (ERP) and other monitoring methods. Traditional ASD psychotherapy mostly focuses on behavioral rehabilitation training, supplemented by some drug treatment.Advanced spatial information technology has certain advantages and potentials for the treatment of autism spectrum disorders.However, at present, the research in this field is relatively scattered and cannot be popularized.