Pubmed du 25/04/20

samedi 25 avril 2020

1. Athar YM, Joseph S. RNA-Binding Specificity of the Human Fragile X Mental Retardation Protein. Journal of molecular biology. 2020.

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and is caused by a deficiency of the fragile X mental retardation protein (FMRP) in neurons. FMRP regulates the translation of numerous mRNAs within dendritic synapses, but how FMRP recognizes these target mRNAs remains unknown. FMRP has KH0, KH1, KH2, and RGG domains, which are thought to bind to specific RNA recognition elements (RREs). Several studies used high-throughput methods to identify various RREs in mRNAs that FMRP may bind to in vivo. However, there is little overlap in the mRNA targets identified by each study, suggesting that the RNA-binding specificity of FMRP is still unknown. To determine the specificity of FMRP for the RREs, we performed quantitative in vitro RNA binding studies with various constructs of human FMRP. Unexpectedly, our studies show that the KH domains do not bind to the previously identified RREs. To further investigate the RNA-binding specificity of FMRP, we developed a new method called Motif Identification by Analysis of Simple sequences (MIDAS) to identify single-stranded RNA (ssRNA) sequences bound by KH domains. We find that the FMRP KH0, KH1, and KH2 domains bind weakly to the ssRNA sequences suggesting that they may have evolved to bind more complex RNA structures. Additionally, we find that the RGG motif of human FMRP binds with a high affinity to an RNA G-quadruplex (GQ) structure that lacks single-stranded loops, double-stranded stems, or junctions.

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2. Ayaydin H, Kirmit A, Celik H, Akaltun I, Koyuncu I, Bilgen Ulgar S. High Serum Levels of Serum 100 Beta Protein, Neuron-specific Enolase, Tau, Active Caspase-3, M30 and M65 in Children with Autism Spectrum Disorders. Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology. 2020 ; 18(2) : 270-8.

Objective : The purpose of this study was therefore to investigate whether neuronal, axonal, and glial cell markers (Neuron-specific enolase [NSE], tau, serum 100 beta protein [S100B], respectively) and apoptosis markers (active caspase 3, M30, M65) and whether these parameters can be used as diagnostic biomarkers in autism spectrum disorders (ASD). Methods : This study measured the serum S100B, NSE, tau, active caspase 3, M30, and M65 levels in 43 patients with ASD (aged 3-12 years) and in 41 age- and sex-matched healthy controls. ASD severity was rated using the Childhood Autism Rating Scale. The serum levels were determined in the biochemistry laboratory using the ELISA technique. The receiver operator characteristics curve method was employed to evaluate the accuracy of the parameters in diagnosing ASD. Results : Serum S100B, tau, NSE, active caspase-3, M30, and M65 levels were significantly higher in the patient group than in the control group (p 0.001, p = 0.002, p = 0.002, p = 0.005, p 0.001, and p = 0.004, respectively). The cut-off value of S100B was 48.085 pg/ml (sensitivity : 74.4%, specificity : 80.5%, areas under the curve : 0.879, p 0.001). Conclusion : Apoptosis increased in children with ASD, and neuronal, axonal, and glial cell injury was observed. In addition, S100B may be an important diagnostic biomarker in patients with ASD. Apoptosis, and neuronal, axonal and astrocyte pathologies may play a significant role in the pathogenesis of ASD, and further studies are now required to confirm this.

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3. Baron-Mendoza I, Gonzalez-Arenas A. Relationship between the effect of polyunsaturated fatty acids (PUFAs) on brain plasticity and the improvement on cognition and behavior in individuals with autism spectrum disorder. Nutr Neurosci. 2020 : 1-24.

Objective : This work aimed to compile information about the neuronal processes in which polyunsaturated fatty acids (PUFAs) could modulate brain plasticity, in order to analyze the role of nutritional intervention with the omega-3 and omega-6 fatty acids as a therapeutic strategy for the Autism Spectrum Disorder (ASD)-related signs and symptoms.Methods : We reviewed different articles reporting the effect of PUFAS on neurite elongation, membrane expansion, cytoskeleton rearrangement and neurotransmission, considering the ASD-related abnormalities in these processes.Results : In accordance to the reviewed studies, it is clear that ASD is one of the neurological conditions associated with an impairment in neuronal plasticity ; therefore, PUFAs-rich diet improvements on cognition and behavioral deficits in individuals with autism, could be involved with the regulation of neuronal processes implicated in the atypical brain plasticity related with this neurodevelopmental disorder.Discussion : The behavioral and cognitive improvement observed in individuals with ASD after PUFAs treatment might underlie, at least in part, in the ability of omega-3 and omega-6 fatty acids to induce neurite outgrowth, probably, through the dynamic regulation of the neuronal cytoskeleton along with the expansion of neuronal membranes. Furthermore, it might also be associated with an enhancement of the efficacy of synaptic transmission and the modulation of neurotransmitters release.

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4. Begum Ali J, Charman T, Johnson MH, Jones EJH. Early Motor Differences in Infants at Elevated Likelihood of Autism Spectrum Disorder and/or Attention Deficit Hyperactivity Disorder. J Autism Dev Disord. 2020.

We investigated infant’s manual motor behaviour ; specifically behaviours crossing the body midline. Infants at elevated likelihood of Autism Spectrum Disorder (ASD) and/or Attention Deficit Hyperactivity Disorder (ADHD) produced fewer manual behaviours that cross the midline compared to infants with a typical likelihood of developing these disorders ; however this effect was limited to 10-month-olds and not apparent at age 5 and 14 months. Although, midline crossing did not predict ASD traits, it was related to ADHD traits at 2 years of age. We rule out motor ability and hand dominance as possible explanations for this pattern of behaviour, positing that these results may be a consequence of multisensory integration abilities, and the neurobehavioural shift period, in the first year of life.

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5. Brito AR, Vairo GPT, Dias A, Olej B, Nascimento OJM, Vasconcelos MM. Effect of prednisolone on language function in children with autistic spectrum disorder : a randomized clinical trial. J Pediatr (Rio J). 2020.

OBJECTIVE : To describe the effect of prednisolone on language in children with autism spectrum disorder. This study is based upon two hypotheses : autism etiology may be closely related to neuroinflammation ; and, an effective treatment should restore the individual’s language skills. METHOD : This is a prospective, double-blinded, randomized, placebo-controlled clinical trial, carried out in a federal university hospital. The initial patient sample consisted of 40 subjects, which were randomized into two parallel groups. Inclusion criteria were : male gender, 3-7 years of age, and meeting the Diagnostic and Statistical Manual of Mental Disorders - 4th edition (DSM-IV) diagnostic criteria. The final sample consisted of 38 patients, of whom 20 were randomized to the placebo group and 18 to the active group. The latter received prednisolone for 24 weeks, at an initial dose of 1mg/kg/day and a tapering dose from the ninth week onward. Language was measured on four occasions over a 12-month period by applying two Brazilian tools : the Language Development Assessment (ADL) and the Child Language Test in Phonology, Vocabulary, Fluency, and Pragmatics (ABFW). RESULTS : The side effects were mild : two patients had hypertension, five had hyperglycemia, and two had varicella. Prednisolone increased the global ADL score in children younger than 5 years of age who had developmental regression (p=0.0057). The ABFW’s total of communicative acts also responded favorably in those participants with regression (p=0.054). The ABFW’s total of vocal acts showed the most significant results, especially in children younger than 5 years (p=0.004, power=0.913). CONCLUSIONS : The benefit of prednisolone for language scores was more evident in participants who were younger than five years, with a history of developmental regression, but the trial’s low dose may have limited this benefit. The observed side effects do not contraindicate corticosteroid use in autism.

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6. Bundgaard-Nielsen C, Knudsen J, Leutscher PDC, Lauritsen MB, Nyegaard M, Hagstrom S, Sorensen S. Gut microbiota profiles of autism spectrum disorder and attention deficit/hyperactivity disorder : A systematic literature review. Gut microbes. 2020 : 1-16.

Accumulating evidence has implicated an involvement of the gut-brain axis in autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD), however with highly diverse results. This systematic review aims to describe and evaluate studies investigating the gut microbiota composition in individuals with ASD or ADHD and to evaluate if variations in gut microbiota are associated with these disorders.Twenty-four articles were identified in a systematic literature search of PubMed and Embase up to July 22, 2019. They consisted of 20 studies investigating ASD and four studies investigating ADHD. For ASD, several studies agreed on an overall difference in beta-diversity, although no consistent bacterial variation between all studies was reported. For ADHD, the results were more diverse, with no clear differences observed.Several common characteristics in gut microbiota function were identified for ASD compared to controls. In contrast, highly heterogeneous results were reported for ADHD, and thus the association between gut microbiota composition and ADHD remains unclear. For both disorders, methodological differences hampered the comparison of studies.

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7. Jaramillo TC, Xuan Z, Reimers JM, Escamilla CO, Liu S, Powell CM. Early restoration of Shank3 expression in Shank3 knockout mice prevents core ASD-like behavioural phenotypes. eNeuro. 2020.

Several genes are associated with increased risk for ASD (Autism Spectrum Disorder), neurodevelopmental disorders that present with repetitive movements and restricted interests along with deficits in social interaction/communication. While genetic alterations associated with ASD are present early in life, ASD-like behaviors are difficult to detect in early infancy. This raises the issue of whether reversal of an ASD-associated genetic alteration early in life can prevent the onset of ASD-like behaviors. Genetic alterations of SHANK3, a well-characterized gene encoding a postsynaptic scaffolding protein, are estimated to contribute to approximately 0.5% of ASD and remain one of the more replicated and well-characterized genetic defects in ASD. Here we investigate whether early genetic reversal of a Shank3 mutation can prevent the onset of ASD-like behaviors in a mouse model. Previously, we have demonstrated that mice deficient in Shank3 display a wide range of behavioral abnormalities such as repetitive grooming, social deficits, anxiety, and motor abnormalities. In this study, we replicate many of these behaviors in Shank3 mutant mice. With early genetic restoration of wild-type Shank3, we rescue behaviors including repetitive grooming and social, locomotor, and rearing deficits. Our findings support the idea that the underlying mechanisms involving ASD behaviors in mice deficient in Shank3 are susceptible to early genetic correction of Shank3 mutations.Significance Statement Rare, de novo, single gene copy number variants and mutations are known causes of autism. The SHANK3 gene is among the most common and replicated genetic causes of autism. With the advent of gene therapy, interest is growing in understanding whether genetic animal models of autism can have their phenotypes ameliorated by genetic reversal. This study confirms that early genetic restoration of a Shank3 mutant mouse model can ameliorate behavioral symptoms with face validity for autism.

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8. Kinnaird E, Dandil Y, Li Z, Smith K, Pimblett C, Agbalaya R, Stewart C, Tchanturia K. Pragmatic Sensory Screening in Anorexia Nervosa and Associations with Autistic Traits. J Clin Med. 2020 ; 9(4).

BACKGROUND : Research suggests that people with anorexia nervosa (AN) experience subjective hypersensitivity to external sensations that may require consideration in treatment. These difficulties may be particularly pronounced in people with AN and high autistic traits. The purpose of this pilot study was to explore the use of a brief screening tool to assess sensory sensitivity in individuals receiving treatment for AN, and to assess if self-rated sensitivity in AN is related to autistic traits. METHODS : 47 individuals receiving treatment for AN completed a brief sensory screening tool and self-rated their autistic traits. Individuals were also asked to give qualitative feedback on the screening tool. RESULTS : People with AN and high autistic traits rated themselves as more hypersensitive compared to people with AN and low autistic traits. Feedback surrounding the use of the screener was positive. CONCLUSIONS : The results of this study suggest that the use of this screener may be beneficial in eating disorder settings to help adjust and calibrate treatment to personal needs, although further research and psychometric evaluation around the clinical use of the screener is required. The finding that people with AN and high autistic traits may experience elevated hypersensitivity also warrants further exploration in future research.

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9. Kitaoka T, Morimoto M, Hashimoto T, Tsuda Y, Nakatsu T, Kyotani S. Evaluation of the efficacy of drug treatment based on measurement of the oxidative stress, using reactive oxygen metabolites and biological antioxidant potential, in children with autism spectrum disorder and attention deficit hyperactivity disorder. Journal of pharmaceutical health care and sciences. 2020 ; 6 : 8.

Background : Autism spectrum disorder (ASD) is a neurodevelopmental disorder, mainly characterized by impairment of social communication and restricted interests. ASD is frequently accompanied by attention deficit hyperactivity disorder (ADHD), which is characterized by carelessness, hyperactivity and impulsivity (ASD/ADHD). It has been suggested that ASD and ADHD are associated with oxidative stress, that is, that patients with ASD/ADHD are in a state of increased oxidative stress. There are currenr tly no objective or biological test criteria for evaluating the efficacy of drug therapy in these patients. The purpose of this study was to evaluate whether oxidative stress markers [serum reactive oxygen metabolites (d-ROMs) levels and biological antioxidant potential (BAP)] can be used as objective indicators for evaluating the efficacy of drug treatment in ASD/ADHD patients. Methods : The subjects of this study subjects were 50 Japanese patients with ASD/ADHD aged 4 to 14 years old. Serum samples were obtained from the patients to measure the serum levels of d-ROMs and the serum BAP. The study subjects were divided into two age groups : preschool children (4 to 6 years old) and school-age children (7 to 14 years old), and the serum levels of d-ROMs, serum BAP, serum BAP/d-ROMs ratio (hereinafter, the prefix serum will be dropped), and scores on the Parent-interview ASD Rating Scales-Text Revision (PARS-TR) and ADHD Rating Scale (ADHD-RS) were determined before and after drug therapy and compared between the two groups. In addition, changes in the d-ROMs, BAP and BAP/d-ROMs ratio and changes in the scores on the PARS-TR and ADHD-RS after treatment were also analyzed. Results : Significant decrease of the d-ROMs, BAP, and scores on the PARS-TR and ADHD-RS, with a significant increase of the BAP/d-ROMs ratio, was observed after treatment. In addition, a significant correlation was observed between the changes in the d-ROMs and changes in the scores on the PARS-TR and ADHD-RS after treatment in the school-age ASD/ADHD children. Conclusion : Our results suggest the possibility that the serum level of d-ROMs may be useful as an objective assessment marker to supplement the subjective assessment of the effects of drug treatment in school-age children with ASD/ADHD.

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10. Krakowski AD, Cost KT, Anagnostou E, Lai MC, Crosbie J, Schachar R, Georgiades S, Duku E, Szatmari P. Inattention and hyperactive/impulsive component scores do not differentiate between autism spectrum disorder and attention-deficit/hyperactivity disorder in a clinical sample. Mol Autism. 2020 ; 11(1) : 28.

BACKGROUND : Although there is high co-occurrence between ASD and ADHD, the nature of this co-occurrence remains unclear. Our study aimed to examine the underlying relationship between ASD and ADHD symptoms in a combined sample of children with a primary clinical diagnosis of ASD or ADHD. METHODS : Participants included children and youth (aged 3-20 years) with a clinical diagnosis of ASD (n = 303) or ADHD (n = 319) for a total of 622 participants. Parents of these children completed the social communication questionnaire (SCQ), a measure of autism symptoms, and the strengths and weaknesses of ADHD and normal behavior (SWAN) questionnaire, a measure of ADHD symptoms. A principal component analysis (PCA) was performed on combined SCQ and SWAN items, followed by a profile analysis comparing normalized component scores between diagnostic groups and gender. RESULTS : PCA revealed a four-component solution (inattention, hyperactivity/impulsivity, social-communication, and restricted, repetitive, behaviors, and interests (RRBI)), with no overlap between SCQ and SWAN items in the components. Children with ASD had higher component scores in social-communication and RRBI than children with ADHD, while there was no difference in inattentive and hyperactive/impulsive scores between diagnostic groups. Males had higher scores than females in social-communication, RRBI, and hyperactivity/impulsivity components in each diagnostic group. LIMITATIONS : We did not formally assess children with ASD for ADHD using our research-criteria for ADHD, and vice versa. High rates of co-occurring ADHD in ASD, for example, may have inflated component scores in inattention and hyperactivity/impulsivity. A disadvantage with using single informant-based reports (i.e., parent-rated questionnaires) is that ASD and ADHD symptoms may be difficult to distinguish by parents, and may be interpreted differently between parents and clinicians. CONCLUSIONS : ASD and ADHD items loaded on separate components in our sample, suggesting that the measurement structure cannot explain the covariation between the two disorders in clinical samples. High levels of inattention and hyperactivity/impulsivity were seen in both ASD and ADHD in our clinical sample. This supports the need for a dimensional framework that examines neurodevelopmental domains across traditional diagnostic boundaries. Females also had lower component scores across social-communication, RRBI, and hyperactivity/impulsivity than males, suggesting that there may be gender-specific phenotypes related to the two conditions.

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11. Mackie TI, Schaefer AJ, Ramella L, Carter AS, Eisenhower A, Jimenez ME, Fettig A, Sheldrick RC. Understanding How Parents Make Meaning of Their Child’s Behaviors During Screening for Autism Spectrum Disorders : A Longitudinal Qualitative Investigation. J Autism Dev Disord. 2020.

A family’s journey in understanding their child’s behaviors in relation to Autism Spectrum Disorders (ASD) frequently begins with screening. This study aimed to characterize the interpretive processes that unfold for parents. We employed longitudinal interviews with 19 families engaged in a community-based multi-stage screening protocol. Parents participated in 1-6 interviews dependent upon children’s length of engagement in the screening protocol ; data were analyzed through modified grounded theory. Parents who moved towards understanding their child’s behaviors as ASD expressed (1) sensitization to ASD symptoms, (2) differentiation from other developmental conditions, and (3) use of the ASD diagnosis to explain the etiology of concerning behaviors. Identifying interpretive processes involved during ASD screening provides new opportunities for shared decision-making.

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12. Naguy A, Moodliar-Rensburg S, Elbadry H, Elsori DH, Alamiri B. The broad autism phenotype and related endophenotypes- like father, like son !. Asian J Psychiatr. 2020 ; 52 : 102038.

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13. Ramachandran R. A qualitative study on perspective of parents of children with autism on the nature of parent-professional relationship in Kerala, India. Autism. 2020 : 1362361320912156.

LAY ABSTRACT : This study explored the nature of relationship between parents of children with autism and professionals who provide therapy-based services for autism in Kerala, India. Given the shortage of professionally qualified therapists and educators (particularly in the case of autism) in low- and medium-income countries, parent-mediated interventions where professionals and parents work as partners are recommended as an effective means to meet the demand. However, for parent-mediated interventions to be effective, we first need to understand the customary nature of parent-professional relationship and develop the intervention accordingly. It is within this context that parents of 21 children with autism whose age ranged between 5.8 and 17.3 years were interviewed in order to understand the customary nature of parent-professional relationship. There was a dearth of scheduled, in-depth, and personalized one-on-one interaction between the parent and the professional. Though parents were involved hands on in their child’s training under professional direction, they remained mere information providers in decision making. The parent-professional relationship did not nurture parent’s self efficacy. This led to parents feeling inadequate to provide for their child’s developmental needs and being apprehensive about adulthood. The customary nature of parent-professional relationship observed may be a reflection of the collectivist culture in India. The findings suggest that parent-mediated interventions will need to focus on enabling parents to break cultural barriers that might be holding them back from partnering with professionals as equals.

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14. Rontani P, Perche O, Greetham L, Jullien N, Gepner B, Feron F, Nivet E, Erard-Garcia M. Impaired expression of the COSMOC/MOCOS gene unit in ASD patient stem cells. Mol Psychiatry. 2020.

Autism spectrum disorders (ASD) are complex neurodevelopmental disorders with a very large number of risk loci detected in the genome. However, at best, each of them explains rare cases, the majority being idiopathic. Genomic data on ASD derive mostly from post-mortem brain analyses or cell lines derived from blood or patient-specific induced pluripotent stem cells (iPSCS). Therefore, the transcriptional and regulatory architecture of the nervous system, particularly during early developmental periods, remains highly incomplete. To access the critical disturbances that may have occurred during pregnancy or early childhood, we recently isolated stem cells from the nasal cavity of anesthetized patients diagnosed for ASD and compared them to stem cells from gender-matched control individuals without neuropsychiatric disorders. This allowed us to discover MOCOS, a non-mutated molybdenum cofactor sulfurase-coding gene that was under-expressed in the stem cells of most ASD patients of our cohort, disturbing redox homeostasis and synaptogenesis. We now report that a divergent transcription upstream of MOCOS generates an antisense long noncoding RNA, to which we coined the name COSMOC. Surprisingly, COSMOC is strongly under-expressed in all ASD patients of our cohort with the exception of a patient affected by Asperger syndrome. Knockdown studies indicate that loss of COSMOC reduces MOCOS expression, destabilizes lipid and energy metabolisms of stem cells, but also affects neuronal maturation and splicing of synaptic genes. Impaired expression of the COSMOC/MOCOS bidirectional unit might shed new lights on the origins of ASD that could be of importance for future translational studies.

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15. Sanders K, Staubitz J, Juarez AP, Marler S, Browning W, McDonnell E, Altstein L, Macklin EA, Warren Z. Addressing Challenging Behavior During Hospitalizations for Children with Autism : A Pilot Applied Behavior Analysis Randomized Controlled Trial. Autism Res. 2020.

This study evaluated the feasibility, acceptance, and potential clinical benefit of brief applied behavior analysis (ABA)-based interventions for children and adolescents with autism spectrum disorder (ASD) displaying challenging behaviors during hospitalizations. Participants included 36 children diagnosed with ASD, 6-17 years of age, who were medically or psychiatrically hospitalized. Children in the intervention group received a brief ABA intervention and were compared to children in the evaluation and monitoring-only group. Families and staff recommended the intervention, children receiving the intervention demonstrated significantly more improvement in unblinded ratings of clinical severity, data from physicians indicated a positive effect of the intervention on levels of staffing and restraints and attending medical providers universally reported satisfaction and benefit of the intervention. Improvements in challenging behaviors were not significantly different as reported by parents, and the length of hospitalization did not differ between the groups. Ultimately, the outcomes of this pilot study suggest incorporating specialized ABA-based assessment and intervention during hospitalization may be feasible and well accepted by clinicians and families. However, future research must address potent methodological challenges related to capturing meaningful data during hospitalizations in order to answer questions of ultimate pragmatic, clinical, and system-level benefits. Trial Registration ClinicalTrials.gov Identifier NCT02339935, Registered 16 January 2015, First participant consented 23 February 2015. Autism Res 2020. (c) 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : Inpatient hospitalizations for children with autism spectrum disorder (ASD) and severe behavior are common, challenging, and costly in terms of human experience. This study evaluated the benefit of brief applied behavior analysis-based interventions to children and adolescents with ASD displaying challenging behaviors during hospitalizations. Families and staff evaluating the procedures noted perceived potential benefits of the intervention, but this initial pilot study did not document changes in hospitalization length or blinded rating of improvement.

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16. Sharna SS, Balasuriya GK, Hosie S, Nithianantharajah J, Franks AE, Hill-Yardin EL. Altered Caecal Neuroimmune Interactions in the Neuroligin-3(R451C) Mouse Model of Autism. Frontiers in cellular neuroscience. 2020 ; 14 : 85.

The intrinsic nervous system of the gut interacts with the gut-associated lymphoid tissue (GALT) via bidirectional neuroimmune interactions. The caecum is an understudied region of the gastrointestinal (GI) tract that houses a large supply of microbes and is involved in generating immune responses. The caecal patch is a lymphoid aggregate located within the caecum that regulates microbial content and immune responses. People with Autism Spectrum Disorder (ASD ; autism) experience serious GI dysfunction, including inflammatory disorders, more frequently than the general population. Autism is a highly prevalent neurodevelopmental disorder defined by the presence of repetitive behavior or restricted interests, language impairment, and social deficits. Mutations in genes encoding synaptic adhesion proteins such as the R451C missense mutation in neuroligin-3 (NL3) are associated with autism and impair synaptic transmission. We previously reported that NL3(R451C) mice, a well-established model of autism, have altered enteric neurons and GI dysfunction ; however, whether the autism-associated R451C mutation alters the caecal enteric nervous system and immune function is unknown. We assessed for gross anatomical changes in the caecum and quantified the proportions of caecal submucosal and myenteric neurons in wild-type and NL3(R451C) mice using immunofluorescence. In the caecal patch, we assessed total cellular density as well as the density and morphology of Iba-1 labeled macrophages to identify whether the R451C mutation affects neuro-immune interactions. NL3(R451C) mice have significantly reduced caecal weight compared to wild-type mice, irrespective of background strain. Caecal weight is also reduced in mice lacking Neuroligin-3. NL3(R451C) caecal ganglia contain more neurons overall and increased numbers of Nitric Oxide (NO) producing neurons (labeled by Nitric Oxide Synthase ; NOS) per ganglion in both the submucosal and myenteric plexus. Overall caecal patch cell density was unchanged however NL3(R451C) mice have an increased density of Iba-1 labeled enteric macrophages. Macrophages in NL3(R451C) were smaller and more spherical in morphology. Here, we identify changes in both the nervous system and immune system caused by an autism-associated mutation in Nlgn3 encoding the postsynaptic cell adhesion protein, Neuroligin-3. These findings provide further insights into the potential modulation of neural and immune pathways.

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17. Shen Y, Li Y, Shi L, Liu M, Wu R, Xia K, Zhang F, Ou J, Zhao J. Autism spectrum disorder and severe social impairment associated with elevated plasma interleukin-8. Pediatr Res. 2020.

BACKGROUND : Autism spectrum disorder (ASD) is a neurodevelopmental disorder with an unclear etiology and pathophysiology. Previous studies have indicated that the dysregulation of cytokines may be involved in the pathogenesis of ASD and that the levels of cytokines may serve as potential biomarkers of this disorder. METHODS : The current study employed a family triad-based case-control design to study the levels of plasma cytokines in families with ASD (n = 45 triads) and controls (n = 38 triads) with a Human Cytokine Twenty-Five-Plex Kit. The Social Responsiveness Scale (SRS) was used to measure social impairment of ASD children. RESULTS : After controlling for the levels of parental cytokines, we identified that interferon-alpha (IFN-alpha), interleukin-7 (IL-7), IL-8, IFN-gamma-inducible protein-10, and macrophage inflammatory protein-1beta were associated with ASD, and IL-8 was the only cytokine also associated with the levels of both parental cytokines in the offspring-parents regression analysis and three subdomains of SRS (social awareness, cognition, and motivations) in the children with ASD. The receiver operating characteristic curve showed that the log-transformed IL-8 level discriminated children with autism from controls with an area under the curve of 0.858 (95% confidence interval : 0.777-0.939). CONCLUSIONS : Our study suggests that IL-8 is a potential biomarker for ASD and may be involved in the pathogenesis of ASD. IMPACT : The study suggests that IL-8 is a promising biomarker for ASD and may be involved in the pathogenesis of ASD.Only a very few studies have reported the parental cytokine levels. The significant strength of this article is that we applied the family triad-based approach to explore cytokine levels in families with autism and controls.There are no objective biomarkers, making the accurate diagnosis, prognostic prediction and effective treatment difficult, and our study provides promising results.

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18. Song L, Luo X, Jiang Q, Chen Z, Zhou L, Wang D, Chen A. Vitamin D Supplementation is Beneficial for Children with Autism Spectrum Disorder : A Meta-analysis. Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology. 2020 ; 18(2) : 203-13.

Objective : We conducted a meta-analysis of randomized controlled trials to explore whether vitamin D supplementation is beneficial for symptom improvement in children with autism spectrum disorder. Methods : We systematically searched the PubMed database, EMBASE, Cochrane Library, Web of Science, Sino-Med, Wanfang Data, and China National Knowledge Infrastructure mainly up to September 2019. Using a fixed effects model, we calculated the standard mean difference with 95% confidence interval. Furthermore, we analyzed baseline serum 25-hydroxyvitamin D levels and outcome scores including the Social Responsiveness Scale and Child Autism Rating Scale scores after vitamin D supplementation. Results : There was no significant difference in baseline serum 25-hydroxyvitamin D levels among 203 children included from three studies in the meta-analysis. After vitamin D supplementation, the outcome scores in the experimental group were dramatically elevated compared with those in the control group (p = 0.03). Conclusion : Vitamin D supplementation improves the typical symptoms of autism spectrum disorder, as indicated by reduced Social Responsiveness Scale and Child Autism Rating Scale scores ; thus, it is beneficial for children with autism spectrum disorder.

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19. Suzuki T, Miyaki K, Tsutsumi A. Which autistic traits are related to depressive symptoms in Japanese workers ?. Industrial health. 2020.

Individuals with autism spectrum disorders are at a high risk of experiencing depressive symptoms. However, the relationship between autistic traits and depressive symptoms is unclear. This study aimed to identify which autistic traits are related to depressive symptoms in Japanese workers. The study participants included 2,049 workers from all areas of Japan. Autistic traits and depressive symptoms were measured using an abridged Japanese version of the Autism-Spectrum Quotient (AQ-Short) and the Japanese version of the K6 scale, respectively. The AQ-Short comprises five autistic trait subcomponents that assess fascination for numbers/patterns, difficulties with imagination, preference for routine, difficulties with social skills, and attention-switching difficulties. Linear regression analyses were performed to estimate the association between total and subcomponent autistic trait scores and depressive symptoms. Participants with higher total autistic trait scores were significantly more likely to have depressive symptoms (p<0.001). When scores on the five autistic trait subcomponents were entered simultaneously into the model, participants with higher scores on all subcomponents other than ’difficulties with imagination’ were significantly more likely to report depressive symptoms. Total autistic traits and autistic trait subcomponents could be used for early detection of the risk of depressive symptoms.

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20. Xiang D, Lu J, Wei C, Cai X, Wang Y, Liang Y, Xu M, Wang Z, Liu M, Wang M, Liang X, Li L, Yao P. Berberine Ameliorates Prenatal Dihydrotestosterone Exposure-Induced Autism-Like Behavior by Suppression of Androgen Receptor. Frontiers in cellular neuroscience. 2020 ; 14 : 87.

Many epidemiology studies have shown that maternal polycystic ovary syndrome (PCOS) results in a greater risk of autism spectrum disorders (ASD) development, although the detailed mechanism remains unclear. In this study, we aimed to investigate the potential mechanism and provide a possible treatment for PCOS-mediated ASD through three experiments : Experiment 1 : real-time PCR and western blots were employed to measure gene expression in human neurons, and the luciferase reporter assay and chromatin immunoprecipitation (ChIP) was used to map the responsive elements on related gene promoters. Experiment 2 : pregnant dams were prenatally exposed to dihydrotestosterone (DHT), androgen receptor (AR) knockdown (shAR) in the amygdala, or berberine (BBR), and the subsequent male offspring were used for autism-like behavior (ALB) assay followed by biomedical analysis, including gene expression, oxidative stress, and mitochondrial function. Experiment 3 : the male offspring from prenatal DHT exposed dams were postnatally treated by either shAR or BBR, and the offspring were used for ALB assay followed by biomedical analysis. Our findings showed that DHT treatment suppresses the expression of estrogen receptor beta (ERbeta) and superoxide dismutase 2 (SOD2) through AR-mediated hypermethylation on the ERbeta promoter, and BBR treatment suppresses AR expression through hypermethylation on the AR promoter. Prenatal DHT treatment induces ERbeta suppression, oxidative stress and mitochondria dysfunction in the amygdala with subsequent ALB behavior in male offspring, and AR knockdown partly diminishes this effect. Furthermore, both prenatal and postnatal treatment of BBR partly restores prenatal DHT exposure-mediated ALB. In conclusion, DHT suppresses ERbeta expression through the AR signaling pathway by hypermethylation on the ERbeta promoter, and BBR restores this effect through AR suppression. Prenatal DHT exposure induces ALB in offspring through AR-mediated ERbeta suppression, and both prenatal and postnatal treatment of BBR ameliorates this effect. We conclude that BBR ameliorates prenatal DHT exposure-induced ALB through AR suppression, this study may help elucidate the potential mechanism and identify a potential treatment through using BBR for PCOS-mediated ASD.

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