1. Behavioral Management of Children With Autism in the Emergency Department. Pediatric emergency care. 2023; 39(1): 51-2.

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2. Adaralegbe NJ, Okobi OE, ZT OO, Segun E, Evbayekha EO, Abolurin A, Egberuare EO, Ezegbe HC, Adegbosin A, Adedeji AG, Angaye EG, Izundu IC, Oyelade BO. Impact of Adverse Childhood Experiences on Resilience and School Success in Individuals With Autism Spectrum Disorder and Attention-Deficit Hyperactivity Disorder. Cureus. 2022; 14(11): e31907.

Adolescents with emotional and behavioral disorders face known academic challenges and poor life outcomes. It was imperative to explore and find if the new diagnostic criterion for diagnosing autism profoundly affects educational outcomes and resilience in individuals diagnosed with co-occurring autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). The literature is robust on the impact of adverse childhood experiences (ACEs) on educational outcomes and resilience in adolescents with no history of disability. Still, there remains a dearth of literature explaining, with no ambiguity, the complex relationships between ACEs and resilience, school engagement, and success in individuals with co-occurring ASD and ADHD. This study reviews the existing scholarships on the topic. The significance of this review is that it informs healthcare providers, rehabilitation counselors, and educators about the need for early identification of individuals with ASD and ADHD with a background in ACEs. This will enable interventions early enough to ensure they are more resilient and can obtain improved success in school-related and outside-school activities and eventually improved quality of life.

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3. Amaral DG. Language in Autism Research: Accurate and Respectful. Autism research : official journal of the International Society for Autism Research. 2022.

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4. Andrews GP, Qian K, Jacobs E, Jones DS, Tian Y. High Drug Loading Nanosized Amorphous Solid Dispersion (NASD) with Enhanced in vitro Solubility and Permeability: Benchmarking conventional ASD. International journal of pharmaceutics. 2022: 122551.

Through liquid-liquid phase separation (LLPS), it is possible to generate drug-rich nanoparticles during the dissolution of conventional amorphous solid dispersions (ASDs). These self-generated nanoparticles may improve the oral absorption of poorly water-soluble drugs by enhancing the drug’s apparent solubility and effective membrane permeability. However, due to the high concentration threshold required for LLPS, conventional ASDs that can consistently generate drug-rich nanoparticles during dissolution are rare. More importantly, the quality of these meta-stable drug-rich nanoparticles is hard to control during dissolution, leading to inconsistency in formulation performances. This work has described a continuous twin-screw extrusion process capable of producing nanosized ASD (NASD) formulations that can offer better solubility and permeability enhancements over conventional ASD formulations. Two polymeric carriers, polyvinylpyrrolidone-co-vinyl acetate (PVPVA) and hydroxypropyl methylcellulose acetate succinate (HPMCAS), with a model hydrophobic drug celecoxib (BCS II), were formulated into both ASD and NASD formulations. Compared to the conventional ASD formulation, the prefabricated NASD (sizes ranging between 40 to 200 nm) embedded within a polyol matrix can be rapidly dispersed into a nanoparticle suspension in the presence of aqueous media. The resulting NASDs achieved drug loadings up to 80% w/w and a maximum of 98% encapsulation efficiency. Because of the TSE platform’s high drug-loading capacity and high scalability, the developed method may be useful for continuously producing personalized nanomedicines.

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5. Angeletos Chrysaitis N, Seriès P. 10 years of Bayesian theories of autism:a comprehensive review. Neuroscience and biobehavioral reviews. 2022: 105022.

Ten years ago, Pellicano and Burr published one of the most influential articles in the study of autism spectrum disorders, linking them to aberrant Bayesian inference processes in the brain. In particular, they proposed that autistic individuals are less influenced by their brains’ prior beliefs about the environment. In this systematic review, we investigate if this theory is supported by the experimental evidence. To that end, we collect all studies which included comparisons across diagnostic groups or autistic traits and categorise them based on the investigated priors. Our results are highly mixed, with a slight majority of studies finding no difference in the integration of Bayesian priors. We find that priors developed during the experiments exhibited reduced influences more frequently than priors acquired previously, with various studies providing evidence for learning differences between participant groups. Finally, we focus on the methodological and computational aspects of the included studies, showing low statistical power and often inconsistent approaches. Based on our findings, we propose guidelines for future research.

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6. Auvinen P, Vehviläinen J, Marjonen H, Modhukur V, Sokka J, Wallén E, Rämö K, Ahola L, Salumets A, Otonkoski T, Skottman H, Ollikainen M, Trokovic R, Kahila H, Kaminen-Ahola N. Chromatin modifier developmental pluripotency associated factor 4 (DPPA4) is a candidate gene for alcohol-induced developmental disorders. BMC medicine. 2022; 20(1): 495.

BACKGROUND: Prenatal alcohol exposure (PAE) affects embryonic development, causing a variable fetal alcohol spectrum disorder (FASD) phenotype with neuronal disorders and birth defects. We hypothesize that early alcohol-induced epigenetic changes disrupt the accurate developmental programming of embryo and consequently cause the complex phenotype of developmental disorders. To explore the etiology of FASD, we collected unique biological samples of 80 severely alcohol-exposed and 100 control newborns at birth. METHODS: We performed genome-wide DNA methylation (DNAm) and gene expression analyses of placentas by using microarrays (EPIC, Illumina) and mRNA sequencing, respectively. To test the manifestation of observed PAE-associated DNAm changes in embryonic tissues as well as potential biomarkers for PAE, we examined if the changes can be detected also in white blood cells or buccal epithelial cells of the same newborns by EpiTYPER. To explore the early effects of alcohol on extraembryonic placental tissue, we selected 27 newborns whose mothers had consumed alcohol up to gestational week 7 at maximum to the separate analyses. Furthermore, to explore the effects of early alcohol exposure on embryonic cells, human embryonic stem cells (hESCs) as well as hESCs during differentiation into endodermal, mesodermal, and ectodermal cells were exposed to alcohol in vitro. RESULTS: DPPA4, FOXP2, and TACR3 with significantly decreased DNAm were discovered-particularly the regulatory region of DPPA4 in the early alcohol-exposed placentas. When hESCs were exposed to alcohol in vitro, significantly altered regulation of DPPA2, a closely linked heterodimer of DPPA4, was observed. While the regulatory region of DPPA4 was unmethylated in both control and alcohol-exposed hESCs, alcohol-induced decreased DNAm similar to placenta was seen in in vitro differentiated mesodermal and ectodermal cells. Furthermore, common genes with alcohol-associated DNAm changes in placenta and hESCs were linked exclusively to the neurodevelopmental pathways in the enrichment analysis, which emphasizes the value of placental tissue when analyzing the effects of prenatal environment on human development. CONCLUSIONS: Our study shows the effects of early alcohol exposure on human embryonic and extraembryonic cells, introduces candidate genes for alcohol-induced developmental disorders, and reveals potential biomarkers for prenatal alcohol exposure.

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7. Butler LK, Tager-Flusberg H. Fine motor skill and expressive language in minimally verbal and verbal school-aged autistic children. Autism research : official journal of the International Society for Autism Research. 2022.

Fine motor skill is associated with expressive language outcomes in infants who have an autistic sibling and in young autistic children. Fewer studies have focused on school-aged children even though around 80% have motor impairments and 30% remain minimally verbal (MV) into their school years. Moreover, expressive language is not a unitary construct, but it is made up of components such as speech production, structural language, and social-pragmatic language use. We used natural language sampling to investigate the relationship between fine motor and speech intelligibility, mean length of utterance and conversational turns in MV and verbal autistic children between the ages of 4 and 7 while controlling for age and adaptive behavior. Fine motor skill predicted speech production, measured by percent intelligible utterances. Fine motor skill and adaptive behavior predicted structural language, measured by mean length of utterance in morphemes. Adaptive behavior, but not fine motor skill, predicted social-pragmatic language use measured by number of conversational turns. Simple linear regressions by group corrected for multiple comparisons showed that fine motor skill predicted intelligibility for MV but not verbal children. Fine motor skill and adaptive behavior predicted mean length of utterance for both MV and verbal children. These findings suggest that future studies should explore whether MV children may benefit from interventions targeting fine motor along with speech and language into their school years.

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8. D’Elia A, Schiavi S, Manduca A, Rava A, Buzzelli V, Ascone F, Orsini T, Putti S, Soluri A, Galli F, Soluri A, Mattei M, Cicconi R, Massari R, Trezza V. FMR1 deletion in rats induces hyperactivity with no changes in striatal dopamine transporter availability. Scientific reports. 2022; 12(1): 22535.

Autism Spectrum Disorder (ASD) is a pervasive neurodevelopmental disorder emerging in early life characterized by impairments in social interaction, poor verbal and non-verbal communication, and repetitive patterns of behaviors. Among the best-known genetic risk factors for ASD, there are mutations causing the loss of the Fragile X Messenger Ribonucleoprotein 1 (FMRP) leading to Fragile X syndrome (FXS), a common form of inherited intellectual disability and the leading monogenic cause of ASD. Being a pivotal regulator of motor activity, motivation, attention, and reward processing, dopaminergic neurotransmission has a key role in several neuropsychiatric disorders, including ASD. Fmr1 (Δ)exon 8 rats have been validated as a genetic model of ASD based on FMR1 deletion, and they are also a rat model of FXS. Here, we performed behavioral, biochemical and in vivo SPECT neuroimaging experiments to investigate whether Fmr1 (Δ)exon 8 rats display ASD-like repetitive behaviors associated with changes in striatal dopamine transporter (DAT) availability assessed through in vivo SPECT neuroimaging. At the behavioral level, Fmr1 (Δ)exon 8 rats displayed hyperactivity in the open field test in the absence of repetitive behaviors in the hole board test. However, these behavioral alterations were not associated with changes in striatal DAT availability as assessed by non-invasive in vivo SPECT and Western blot analyses.

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9. Ershova ES, Veiko NN, Nikitina SG, Balakireva EE, Martynov AV, Chudakova JM, Shmarina GV, Kostyuk SE, Salimova NA, Veiko RV, Porokhovnik LN, Asanov AY, Izhevskaia VL, Kutsev SI, Simashkova NV, Kostyuk SV. Ribosomal DNA Abundance in the Patient’s Genome as a Feasible Marker in Differential Diagnostics of Autism and Childhood-Onset Schizophrenia. Journal of personalized medicine. 2022; 12(11).

INTRODUCTION: Differential diagnostics of early-onset schizophrenia and autism spectrum disorders (ASD) are a problem of child psychiatry. The prognosis and relevant treatment are to a large degree determined by the correctness of diagnosis. We found earlier that leucocyte DNA of adult schizophrenia patients contained significantly larger copy numbers of ribosomal repeats (rDNA) coding for rRNA, than DNA of mentally healthy controls. AIM: To compare the contents of ribosomal repeats in the leucocyte DNA of children with schizophrenia, children with ASD, and healthy age-matched controls to estimate the possibility of using this genetic trait in the differential diagnostics of the two types of disorders. PATIENTS AND METHODS: Blood samples of patients with infantile autism (A-F84.0 according to ICD-10, N = 75) and with childhood-onset schizophrenia (SZ-F20.8 according to ICD-10, N = 43) were obtained from the Child Psychiatry Department of the Mental Health Research Center. The healthy control blood samples (HC, N = 86) were taken from the Research Centre for Medical Genetics collection. The recruitment of cases was based on the clinical psychopathologic approach. DNA was extracted from blood leukocytes with organic solvents. Nonradioactive quantitative hybridization technique was applied for determining the abundance of ribosomal repeats in the genomes. Statistical processing was performed using StatPlus, Statgraphics and MedCalc. FINDINGS: DNA derived from SZ cases contained 565 ± 163 rDNA copies, which is significantly (p < 10(-6)) higher than the rDNA content in ASD cases (405 ± 109 copies) and controls (403 ± 86 copies). The HC and A groups did not differ by rDNA copy number (p > 0.4). The genetic trait « rDNA copy number in patient’s genome » can potentially be applied as an additional marker in differential diagnostics of childhood-onset schizophrenia and autism spectrum disorders.

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10. Frye RE, Cakir J, McCarty PJ, Rose S, Delhey LM, Palmer RF, Austin C, Curtin P, Yitshak-Sade M, Arora M. Air Pollution and Maximum Temperature Are Associated with Neurodevelopmental Regressive Events in Autism Spectrum Disorder. Journal of personalized medicine. 2022; 12(11).

Neurodevelopmental regression (NDR) is an enigmatic event associated with autism spectrum disorder (ASD) during which a child loses previously acquired skills and develops ASD symptoms. In some, a trigger which precedes the NDR event, such as a fever, can be identified, but in many cases no trigger is obvious. We hypothesize that air pollution (PM(2.5)) may trigger NDR, especially in those children without an identified trigger. Average daily PM(2.5), ozone, precipitation and maximum temperature (T(max)) were derived from Environmental Protection Agency models and National Oceanic and Atmospheric Administration monitors based on zip-code information from 83 ASD participants during the six-weeks following the onset month of an NDR event and a reference period defined as one year before and one year after the event. Seasonally adjusted logistic regression (LR) and linear mixed models (LMM) compared cases (with a history of NDR) and matched controls (without a history of NDR). LR models found that the risk of NDR was related to higher PM(2.5) during 3 to 6 weeks of the NDR event period, particularly in those without a trigger. Overall, both models converged on NDR being related to a higher PM(2.5) and lower T(max) both during the NDR event period as well as the reference period, particularly in those without a known trigger. This temporal pattern suggests that environmental triggers, particularly PM(2.5), could be related to NDR, especially in those without an identifiable trigger. Further studies to determine the underlying biological mechanism of this observation could help better understand NDR and provide opportunities to prevent NDR.

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11. Jyonouchi H, Geng L, Rossignol DA, Frye RE. Long COVID Syndrome Presenting as Neuropsychiatric Exacerbations in Autism Spectrum Disorder: Insights for Treatment. Journal of personalized medicine. 2022; 12(11).

COVID-19 causes not only severe respiratory symptoms, but also long-term sequelae, even if the acute-phase symptoms are minor. Neurological and neuropsychiatric symptoms are emerging as major long-term sequalae. In patients with pre-existing behavioral symptoms, such as individuals with autism spectrum disorders (ASD), the emergence of neuropsychiatric symptoms due to long COVID can be difficult to diagnose and manage. Herein, we present three ASD cases who presented with markedly worsening neuropsychiatric symptoms following COVID-19 exposure and subsequent difficulty in managing the post-COVID neuropsychiatric symptoms. Case 1 contracted SARS-CoV-2 during the early stages of the pandemic and treatment targeting COVID-19-induced immune activation was delayed. Case 2 was asymptomatic in the acute stage of a confirmed COVID-19 exposure, but still developed significant neuropsychiatric symptoms. Case 3 demonstrated a difficult course, partly due to pre-existing immune dysregulation and prior use of multiple immunomodulating agents. In cases 1 and 3 for whom serial blood samples were obtained, notable changes in the production of inflammatory and counter-regulatory cytokines by peripheral blood monocytes were observed. The presented cases illustrate the profound effects of COVID-19 on neuropsychiatric symptoms in ASD subjects and the difficulty of managing long-COVID symptoms.

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12. Lim M, Carollo A, Neoh MJY, Sacchiero M, Azhari A, Balboni G, Marschik P, Nordahl-Hansen A, Dimitriou D, Esposito G. Developmental disabilities in Africa: A scientometric review. Research in developmental disabilities. 2022; 133: 104395.

BACKGROUND: Developmental disabilities are disproportionately more investigated in higher-income countries. However, global prevalence of developmental disabilities indicate that a large proportion of individuals with disabilities reside in low- and middle-income nations. AIMS: The present work therefore aims to conduct a scientometric review to survey available literature on developmental disabilities in low- and middle-income countries belonging to the continent of Africa. METHODS AND PROCEDURES: A literature search was conducted on Scopus, where a total of 1720 relevant publications (and an accompanying 66 thousand references) were found, representing research conducted between 1950 to 2022. Then, document co-citation analysis was performed to chart significant co-citation relationships between relevant articles and their cited references. OUTCOMES AND RESULTS: The generated network based on document co-citation analysis revealed a total of 14 distinct thematic research clusters and 12 significant documents that have been frequently cited in the literature on developmental disabilities in Africa. CONCLUSIONS AND IMPLICATIONS: The scientometric review revealed a trend of broadening research towards systems of care, away from a medical model of disease. It is projected that future research will continue to capitalise on inter-disciplinary strengths to arrive at a more nuanced understanding of developmental disability from all levels – individuals, families, to communities.

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13. Lovell B, Newman A, Wetherell MA. Seeing it my way: A perspective taking intervention alleviates psychological distress in caregivers of autistic children. Research in developmental disabilities. 2022; 133: 104396.

Cognitively empathic caregivers are able to take the perspective of their autistic child(ren) without experiencing vicarious distressing emotions, and typically report lower psychological distress. Taking the perspective of the autistic child might, through fostering cognitive empathy, might relieve caregivers’ psychological distress. Here we explored whether autism perspective taking videos developed by the National Autistic Society (NAS), intended to raise public awareness about autism, might be effective, packaged as an intervention, for increasing caregivers’ cognitive empathy and reducing their psychological distress. A sample of 24 caregivers of autistic children completed questionnaires capturing psychological distress and cognitive empathy at baseline. For three consecutive days, for two-three minutes per day, caregivers watched perspective taking videos. Follow up assessments were collected 7, 14, and 21 days post intervention. Psychological distress was lower after seven days, and stayed lower 14 and 21 days post intervention compared with baseline. Cognitive empathy was higher after 14 days, and remained higher 21 days post intervention compared with baseline. Taking the perspective of the autistic child, achieved here with publically available NAS videos, seems to be effective for increasing caregivers’ cognitive empathy and reducing their psychological distress for up to three weeks. Future research might use more rigorous methodologies, incorporating control groups and larger samples, to explore moderators of intervention efficacy.

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14. Miclea D, Osan S, Bucerzan S, Stefan D, Popp R, Mager M, Puiu M, Zimbru C, Chirita-Emandi A, Alkhzouz C. Copy number variation analysis in 189 Romanian patients with global developmental delay/intellectual disability. Italian journal of pediatrics. 2022; 48(1): 207.

BACKGROUND: Developmental delay and intellectual disability represent a common pathology in general population, involving about 3% of the pediatric age population, the genetic etiology being often involved. The aim of this study was to determine the clinically relevant copy number variants in patients diagnosed with global developmental delay/intellectual disability in our population, using the chromosomal microarray analysis. METHODS: We analyzed 189 patients diagnosed with global developmental delay/intellectual disability, presented in Clinical Emergency Hospital for Children, Cluj-Napoca. The patients were completely clinically investigated, including dysmorphic and internal malformations evaluation, psychiatric, neuropsychological and metabolic evaluation, standard karyotyping. Genomic analysis was done using chromosomal microarray analysis. RESULTS: Pathogenic findings (including uniparental disomy) and variants of unknown significance were detected in 53 of 189 patients (28.04%). Pathogenic copy number variants and uniparental disomy were observed in 35 of 189 patients (18.51%). Two patients presented uniparental disomy for chromosome 15, one with clinical phenotype of Prader-Willi syndrome and the other with clinical phenotype with Angelman syndrome. Within the category of pathogenic findings, the recurrent copy number variants were seen in 21 of 35 patients (60%). CONCLUSIONS: The increased percentage of pathogenic structural variants observed in patients with global developmental delay/intellectual disability analyzed by chromosomal microarray technique supports its use in patients with a non-specific phenotype such as these neurodevelopmental disorders. The high percentage of recurrent pathogenic variants between these findings is a finding that support their initial evaluation when a genetic testing algorithm could be a useful option.

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15. Santamarina-Siurana C, Cloquell-Ballester V, Berenguer-Forner C, Fuentes-Albero M. Effect of vibrostimulatory wearable technology on stereotyped behaviour in a child with autism and intellectual disability. BMJ case reports. 2022; 15(12).

The aim of the work has been to report on the effects of vibrostimulation, administered through wearable technology, on stereotyped behaviour of a child in middle childhood, with autism, intellectual disability and severe behaviour in the ‘stereotypic behaviour’ subscale of the Restricted and Repetitive Behaviour Revised Scale. He received vibrostimulation (210 Hz, 2.8 µm), with a continuous pattern of vibration: three vibrations of 700 ms, each separated by a rest period of 500 ms and a pause of 8000 ms. Vibration was delivered bilaterally by two devices, repeating the vibration pattern for 3 min. The measures were repeated four times alternately, with the device turned off and on. The outcome measure was frequency of stereotyed behaviour, which was evaluated for 3 min with and without vibrostimulation. The results and observations, over 3 min of stimulation, showed the disappearance of stereotyped movements during vibrostimulation and better precision in intentional hand movements. Subjectively, the child enjoyed vibrostimulation.

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16. Wang Z, Xu Y, Peng D, Gao J, Lu F. Brain functional activity-based classification of autism spectrum disorder using an attention-based graph neural network combined with gene expression. Cerebral cortex (New York, NY : 1991). 2022.

Autism spectrum disorder (ASD) is a complex brain neurodevelopmental disorder related to brain activity and genetics. Most of the ASD diagnostic models perform feature selection at the group level without considering individualized information. Evidence has shown the unique topology of the individual brain has a fundamental impact on brain diseases. Thus, a data-constructing method fusing individual topological information and a corresponding classification model is crucial in ASD diagnosis and biomarker discovery. In this work, we trained an attention-based graph neural network (GNN) to perform the ASD diagnosis with the fusion of graph data. The results achieved an accuracy of 79.78%. Moreover, we found the model paid high attention to brain regions mainly involved in the social-brain circuit, default-mode network, and sensory perception network. Furthermore, by analyzing the covariation between functional magnetic resonance imaging data and gene expression, current studies detected several ASD-related genes (i.e. MUTYH, AADAT, and MAP2), and further revealed their links to image biomarkers. Our work demonstrated that the ASD diagnostic framework based on graph data and attention-based GNN could be an effective tool for ASD diagnosis. The identified functional features with high attention values may serve as imaging biomarkers for ASD.

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17. Wolpert KH, Kodish I, Kim SJ, Uspal NG. Behavioral Management of Children With Autism in the Emergency Department. Pediatric emergency care. 2023; 39(1): 45-50.

Autism spectrum disorder (ASD) is characterized by impaired social communication in conjunction with patterned behaviors. Often associated with emotional dysregulation, irritability, aggression, depression, and suicidality, ASD youth frequently present to the emergency department for behavioral and mental health evaluation. Psychiatric comorbidities, agitation, and depression are commonly encountered. During these visits, practitioners must thoughtfully consider organic etiologies for presenting symptoms, formulate plans to address risk of agitation, and understand how to effectively formulate disposition options in this patient population.

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18. Zheng Y, Prince N, van Hattem C, Garssen J, Pardo PP, Kraneveld AD. The interaction between intestinal bacterial metabolites and phosphatase and tensin homolog in autism spectrum disorder. Molecular and cellular neurosciences. 2022: 103805.

Intestinal bacteria-associated para-cresyl sulfate (pCS) and 4-ethylphenyl sulfate (4EPS) are elevated in autism spectrum disorder (ASD). Both metabolites can induce ASD-like behaviors in mice, but the molecular mechanisms are not known. Phosphatase and tensin homolog (PTEN) is a susceptibility gene for ASD. The present study investigated the relation between pCS and 4EPS and PTEN in ASD in a valproic acid (VPA)-induced murine ASD model and an in vitro LPS-activated microglial model. The VPA-induced intestinal inflammation and compromised permeability in the distal ileum was not associated with changes of PTEN expression and phosphorylation. In contrast, VPA reduced PTEN expression in the hippocampus of mice. In vitro results show that pCS and 4EPS reduced PTEN expression and derailed innate immune response of BV2 microglial cells. The PTEN inhibitor VO-OHpic did not affect innate immune response of microglial cells. In conclusion, PTEN does not play a role in intestinal inflammation and compromised permeability in VPA-induced murine model for ASD. Although pCS and 4EPS reduced PTEN expression in microglial cells, PTEN is not involved in the pCS and 4EPS-induced derailed innate immune response of microglial cells. Further studies are needed to investigate the possible involvement of reduced PTEN expression in the ASD brain regarding synapse function and neuronal connectivity.

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