1. Alhosaini K, Ansari MA, Nadeem A, Bakheet SA, Attia SM, Alhazzani K, Albekairi TH, Al-Mazroua HA, Mahmood HM, Ahmad SF. 5-Aminoisoquinolinone, a PARP-1 Inhibitor, Ameliorates Immune Abnormalities through Upregulation of Anti-Inflammatory and Downregulation of Inflammatory Parameters in T Cells of BTBR Mouse Model of Autism. Brain Sci. 2021 ; 11(2).

Autism spectrum disorder (ASD) covers a range of neurodevelopmental disorders involving impairments in communication and repetitive and stereotyped patterns of behavior and reciprocal social interaction. 5-Aminoisoquinolinone (5-AIQ), a PARP-1 inhibitor, has neuroprotective and anti-inflammatory effects. We investigated the influence of 5-AIQ-treatment in BTBR T+ Itpr3tf/J (BTBR) mice as an autism model and used flow cytometry to assess the effect of 5-AIQ on FOXP3, Helios, GATA3, IL-9, IL-10 and IL-17A production by CXCR6+ and CD4+ T cells in the spleen. We also confirmed the effect of 5-AIQ treatment on expression of FOXP3, Helios, GATA3, IL-17A, IL-10, and IL-9 mRNA and protein expression levels in the brain tissue by quantitative PCR and western blotting. Our results demonstrated that 5-AIQ-treated BTBR mice had significantly increased numbers of CXCR6+FOXP3+, CXCR6+IL-10+, and CXCR6+Helios+ cells and decreased numbers of CD4+GATA3+, CD4+IL-9+, and CD4+IL-17A+ cells as compared with those in untreated BTBR mice. Our results further demonstrated that treatment with 5-AIQ in BTBR mice increased expression for FOXP3, IL-10, and Helios, and decreased expression for GATA3, IL-17A, and IL-9 mRNA. Our findings support the hypotheses that 5-AIQ has promising novel therapeutic effects on neuroimmune dysfunction in autism and is associated with modulation of Treg and Th17 cells.

Lien vers le texte intégral (Open Access ou abonnement)

2. Bürki L, Höfer J, Kamp-Becker I, Poustka L, Roessner V, Stroth S, Wolff N, Hoffmann F, Bachmann C. Special educational support in children and adolescents with Autism Spectrum Disorder in Germany : Results from a parent survey. Res Dev Disabil. 2021 ; 112 : 103931.

OBJECTIVE : Children and adolescents with Autism Spectrum Disorder (ASD) often receive special educational support (SES). This study aimed to evaluate SES prevalence in children and adolescents with ASD in Germany. METHODS : A mail survey was distributed to the caregivers of 637 children and adolescents recruited at three German ASD outpatient clinics. RESULTS : Among the 211 respondents (response : 33.1 %), 82.5 % were provided with a special educational needs statement, and 63.9 % received special education, most of them attending a public special school (57.9 %). The most frequently indicated additional support was a classroom assistant (69.0 %), followed by smaller learning groups (31.7 %). Special education was less frequently provided to individuals with Asperger syndrome than to those with childhood or atypical autism (36.0 %, 76.1 %, and 63.4 %, respectively). Using logistic regression analysis, receiving special education was significantly associated with lower IQ (<85) (Odds Ratio (OR) : 8.72 ; 95 % confidence interval (CI) : 3.41-22.32) and younger age (≤11 years, OR : 2.87 ; 95 % CI : 1.11-7.38), but not with ASD symptom severity. CONCLUSIONS : The majority of children and adolescents with ASD received SES, indicating a satisfactory supply of such services in Germany. The finding that lower IQ but not ASD symptom severity predicted access to SES raises questions about the specificity of the used selection criteria.

Lien vers le texte intégral (Open Access ou abonnement)

3. Cham R, Iverson JM, Bailes AH, Jennings JR, Eack SM, Redfern MS. Attention and sensory integration for postural control in young adults with autism spectrum disorders. Experimental brain research. 2021.

Postural control impairments have been reported in adults with autism spectrum disorders (ASD). Balance relies on the integration of multisensory cues, a process that requires attention. The purpose of this study was to determine if the influence of attention demands on sensory integration abilities relevant for balance partially contributes to postural control impairments in ASD. Young adults with ASD (N = 24) and neurotypical participants (N = 24) were exposed to sensory perturbations during standing. An established dual-task paradigm was used, requiring participants to maintain balance in these sensory challenging environments and to perform auditory information processing tasks (simple reaction time task and choice reaction time task). Balance was assessed using sway magnitude and sway speed, and attention demands were evaluated based on the response time in the auditory tasks. While young adults with ASD were able to maintain balance in destabilizing sensory conditions, they were more challenged (greater sway speed) than their neurotypical counterparts. Additionally, when exposed for an extended amount of time (3 min) to the most challenging sensory condition included in this study, adults with ASD exhibited a reduced ability to adapt their postural control strategies (sway speed was minimally reduced), demonstrating a postural inflexibility pattern in ASD compared to neurotypical counterparts. Finally, the impact of performing an auditory information processing task on balance and the dual-task cost on information processing (response time) was similar in both groups. ASD may disrupt temporal adaptive postural control processes associated with sensory reweighting that occurs in neurotypicals.

Lien vers le texte intégral (Open Access ou abonnement)

4. Defrin R, Benromano T, Pick CG. Specific Behavioral Responses Rather Than Autonomic Responses Can Indicate and Quantify Acute Pain among Individuals with Intellectual and Developmental Disabilities. Brain Sci. 2021 ; 11(2).

Individuals with intellectual and developmental disabilities (IDD) are at a high risk of experiencing pain. Pain management requires assessment, a challenging mission considering the impaired communication skills in IDD. We analyzed subjective and objective responses following calibrated experimental stimuli to determine whether they can differentiate between painful and non-painful states, and adequately quantify pain among individuals with IDD. Eighteen adults with IDD and 21 healthy controls (HC) received experimental pressure stimuli (innocuous, mildly noxious, and moderately noxious). Facial expressions (analyzed with the Facial Action Coding System (FACS)) and autonomic function (heart rate, heart rate variability (HRV), pulse, and galvanic skin response (GSR)) were continuously monitored, and self-reports using a pyramid and a numeric scale were obtained. Significant stimulus-response relationships were observed for the FACS and pyramid scores (but not for the numeric scores), and specific action units could differentiate between the noxious levels among the IDD group. FACS scores of the IDD group were higher and steeper than those of HC. HRV was overall lower among the IDD group, and GSR increased during noxious stimulation in both groups. In conclusion, the facial expressions and self-reports seem to reliably detect and quantify pain among individuals with mild-moderate IDD ; their enhanced responses may indicate increased pain sensitivity that requires careful clinical consideration.

Lien vers le texte intégral (Open Access ou abonnement)

5. Dellapiazza F, Audras-Torrent L, Michelon C, Baghdadli A. Clinical characteristics of children with ASD and comorbid ADHD : Association with social impairment and externalizing and internalizing behaviours. Res Dev Disabil. 2021 ; 113 : 103930.

BACKGROUND : Autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) are frequently occurring conditions that are often associated (ASD + ADHD). However, there are few comparative studies concerning the clinical presentation in patients formally diagnosed with both ASD and ADHD. Here, we aimed to 1) compare social impairment and externalizing/internalizing behavioural problems across four groups of children : ASD + ADHD, ASD alone, ADHD alone, and typical development and 2) examine their bidirectional relationship with ASD and/or ADHD symptoms. METHODS : This study included 186 participants from 6 to 12 years of age : single ASD (n = 98), ASD + ADHD (n = 29), single ADHD (n = 28), and TD (n = 31). RESULTS : The results showed that children in the ASD + ADHD and single ASD groups had a higher level of social impairment than those in the single ADHD group. In addition, children in the single ADHD group presented a greater attention deficit than those in the single ASD group. Externalizing /internalizing behaviours were more frequent in all groups with neuro-developmental disorders than in typical development. In addition, externalizing behavioural problems were related to ADHD severity in the ASD + ADHD and single ADHD groups, whereas internalizing behaviours were related to ASD severity. CONCLUSIONS : These findings highlight the specific needs of children who have both ASD and ADHD and underscore the necessity of individualizing their interventions.

Lien vers le texte intégral (Open Access ou abonnement)

6. Di Renzo M, Guerriero V, Pagnacco A, Petrillo M, Racinaro L, D’Errico S, Bianchi di Castelbianco F. Attunement and Paternal Characteristics in Care Relationships in the Presence of Children Diagnosed with Autism. Int J Environ Res Public Health. 2021 ; 18(4).

Parents of children with autism spectrum disorder (ASD) have to address various challenges mainly due to their children’s atypia related to communication, emotion regulation and behaviors, arising also within the relationship with their caregivers. Several studies have pointed out that children with ASD can exhibit many difficulties regarding initiating and maintaining meaningful relationships with others. To date, little research has explored the interactions between children with ASD and their fathers, focusing more on mothers. In the context of parent-child interactions in the presence of autism, recent studies have highlighted the importance of parental attunement but there is little research considering solely the affective-bodily dimension. Therefore, the aim of the present study was to explore the parental attunement in fathers of children with ASD observed during play interactions and to investigate the relationship between paternal attunement and the perception of their psychological characteristics related to care relationships. The results highlight that fathers who describe themselves as better in affective care and sensitivity toward others more likely have an absence of paternal attunement during play interactions. The data presented are discussed in the light of intervention hypotheses, aimed at improving the relationship between fathers and children with autism.

Lien vers le texte intégral (Open Access ou abonnement)

7. Dierick F, Buisseret F, Eggermont S. Low-Cost Sensors and Biological Signals. Sensors (Basel, Switzerland). 2021 ; 21(4).

Low-cost sensors, i […].

Lien vers le texte intégral (Open Access ou abonnement)

8. Eissa N, Venkatachalam K, Jayaprakash P, Falkenstein M, Dubiel M, Frank A, Reiner-Link D, Stark H, Sadek B. The Multi-Targeting Ligand ST-2223 with Histamine H(3) Receptor and Dopamine D(2)/D(3) Receptor Antagonist Properties Mitigates Autism-Like Repetitive Behaviors and Brain Oxidative Stress in Mice. International journal of molecular sciences. 2021 ; 22(4).

Autism spectrum disorder (ASD) is a complex heterogeneous neurodevelopmental disorder characterized by social and communicative impairments, as well as repetitive and restricted behaviors (RRBs). With the limited effectiveness of current pharmacotherapies in treating repetitive behaviors, the present study determined the effects of acute systemic treatment of the novel multi-targeting ligand ST-2223, with incorporated histamine H(3) receptor (H(3)R) and dopamine D(2)/D(3) receptor affinity properties, on ASD-related RRBs in a male Black and Tan BRachyury (BTBR) mouse model of ASD. ST-2223 (2.5, 5, and 10 mg/kg, i.p.) significantly mitigated the increase in marble burying and self-grooming, and improved reduced spontaneous alternation in BTBR mice (all p < 0.05). Similarly, reference drugs memantine (MEM, 5 mg/kg, i.p.) and aripiprazole (ARP, 1 mg/kg, i.p.), reversed abnormally high levels of several RRBs in BTBR (p < 0.05). Moreover, ST-2223 palliated the disturbed anxiety levels observed in an open field test (all p < 0.05), but did not restore the hyperactivity parameters, whereas MEM failed to restore mouse anxiety and hyperactivity. In addition, ST-2223 (5 mg/kg, i.p.) mitigated oxidative stress status by decreasing the elevated levels of malondialdehyde (MDA), and increasing the levels of decreased glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) in different brain parts of treated BTBR mice (all p < 0.05). These preliminary in vivo findings demonstrate the ameliorative effects of ST-2223 on RRBs in a mouse model of ASD, suggesting its pharmacological prospective to rescue core ASD-related behaviors. Further confirmatory investigations on its effects on various brain neurotransmitters, e.g., dopamine and histamine, in different brain regions are still warranted to corroborate and expand these initial data.

Lien vers le texte intégral (Open Access ou abonnement)

9. Garcia JM, Cathy BS, Garcia AV, Shurack R, Brazendale K, Leahy N, Fukuda D, Lawrence S. Transition of a Judo Program from In-Person to Remote Delivery During COVID-19 for Youth with Autism Spectrum Disorder. Adv Neurodev Disord. 2021 : 1-6.

OBJECTIVES : To examine the feasibility of a remote judo program for high school students with autism spectrum disorder (ASD) during the COVID-19 pandemic. METHODS : Nine high school students with ASD had been participating in an in-person judo program that transitioned to a livestream format once the stay-at-home orders were mandated. The students completed surveys regarding their experience with the remote sessions. Their classroom teacher completed a semi-structured interview regarding the advantages and disadvantages of the remote format. RESULTS : Eight out of the nine students attended 92% of the remote classes. All nine students reported feeling satisfied with the remote judo sessions. Reported benefits of the remote format included the structured routine during the pandemic and the opportunity for physical activity. Disadvantages included a lack of space and lack of one-on-one instruction. CONCLUSIONS : The remote judo program appeared to be both feasible and acceptable for youth with ASD.

Lien vers le texte intégral (Open Access ou abonnement)

10. Lacruz-Pérez I, Sanz-Cervera P, Pastor-Cerezuela G, Gómez-Marí I, Tárraga-Mínguez R. Is It Possible to Educate, Intervene or « Cure » Autism Spectrum Disorder ? A Content Analysis of YouTube Videos. Int J Environ Res Public Health. 2021 ; 18(5).

YouTube is one of the most well-known and widely accessed websites worldwide, thus having a powerful pedagogical potential. Nonetheless, the quality and the veracity of some YouTube videos are questionable. Doubts regarding the trustworthiness of factual content is a controversial factor that needs to be taken into account, especially when addressing public health issues. For this reason, the main objective of this work is to analyze the content of the most viewed videos in Spanish on YouTube related to autism spectrum disorder (ASD). To carry out this research, the terms « autism AND education », « autism AND intervention », and « autism AND cure » were used (in Spanish). The analysis of these searches results indicated that videos included in the « cure » category are shorter, and less valued by internet users, obtaining the lowest ratings on the « Patient Education Materials Assessment Tool » for audiovisual materials (PEMAT-A/V), in addition to present therapies that are in fact more harmful than videos in other categories. In general, videos containing recommendations for therapies that are harmful are the ones that have received most views, along with the videos that include alternative non-harmful therapies. Practical implications of these findings and recommendations for further research are discussed.

Lien vers le texte intégral (Open Access ou abonnement)

11. Maigoro AY, Lee S. Gut Microbiome-Based Analysis of Lipid A Biosynthesis in Individuals with Autism Spectrum Disorder : An In Silico Evaluation. Nutrients. 2021 ; 13(2).

The link between autism spectrum disorder (ASD) and the gut microbiome has received much attention, with special focus on gut-brain-axis immunological imbalances. Gastrointestinal problems are one of the major symptoms of ASD and are thought to be related to immune dysregulation. Therefore, in silico analysis was performed on mined data from 36 individuals with ASD and 21 control subjects, with an emphasis on lipid A endotoxin-producing bacteria and their lipopolysaccharide (LPS) metabolic pathways. Analysis of enzyme distribution among the 15 most abundant genera in both groups revealed that almost all these genera utilized five early-stage enzymes responsible for catalyzing the nine conserved lipid A synthesis steps. However, Haemophilus and Escherichia, which were significantly more abundant in individuals with ASD than in the control subjects, possess a complete set of essential lipid A synthesis enzymes. Furthermore, the 10 genera with the greatest increase in individuals with ASD showed high potential for producing late-stage lipid A products. Collectively, these results suggested that the synthesis rate of immunogenic LPS end products is likely to increase in individuals with ASD, which may be related to their gastrointestinal symptoms and elevated inflammatory conditions.

Lien vers le texte intégral (Open Access ou abonnement)

12. May CD, St George JM, Lane S. Fathers Raising Children on the Autism Spectrum : Lower Stress and Higher Self-Efficacy Following SMS (Text2dads) Intervention. J Autism Dev Disord. 2021.

This study explored potential influence of a text-based program for fathers of children on the autism spectrum. Fathers (N = 184) were recruited through autism services across Australia. Participants received messages focusing on five domains : (a) relationships with parenting partner ; (b) formal support ; (c) father-child interaction ; (d) understanding autism ; and, (e) coping. Surveys explored parenting stress, co-parenting quality and autism-specific parenting self-efficacy. Eighty-eight percent completed the program, 43.6% completed pre and post surveys. There was significant reduction in parenting stress (p < .01) and increase in autism-specific parenting self-efficacy (p < .01). Effect sizes indicate these may be clinically meaningful. This highly scalable intervention has potential to influence factors that shape and sustain relationships fathers share with their children on the autism spectrum, families and services.

Lien vers le texte intégral (Open Access ou abonnement)

13. Nobile V, Pucci C, Chiurazzi P, Neri G, Tabolacci E. DNA Methylation, Mechanisms of FMR1 Inactivation and Therapeutic Perspectives for Fragile X Syndrome. Biomolecules. 2021 ; 11(2).

Among the inherited causes of intellectual disability and autism, Fragile X syndrome (FXS) is the most frequent form, for which there is currently no cure. In most FXS patients, the FMR1 gene is epigenetically inactivated following the expansion over 200 triplets of a CGG repeat (FM : full mutation). FMR1 encodes the Fragile X Mental Retardation Protein (FMRP), which binds several mRNAs, mainly in the brain. When the FM becomes methylated at 10-12 weeks of gestation, the FMR1 gene is transcriptionally silent. The molecular mechanisms involved in the epigenetic silencing are not fully elucidated. Among FXS families, there is a rare occurrence of males carrying a FM, which remains active because it is not methylated, thus ensuring enough FMRPs to allow for an intellectual development within normal range. Which mechanisms are responsible for sparing these individuals from being affected by FXS ? In order to answer this critical question, which may have possible implications for FXS therapy, several potential epigenetic mechanisms have been described. Here, we focus on current knowledge about the role of DNA methylation and other epigenetic modifications in FMR1 gene silencing.

Lien vers le texte intégral (Open Access ou abonnement)

14. Pan CY, Tsai CL, Chen FC, Chow BC, Chen CC, Chu CH. Physical and Sedentary Activity Patterns in Youths with Autism Spectrum Disorder. Int J Environ Res Public Health. 2021 ; 18(4).

Little is known about the patterns of sedentary behavior and physical activity (PA) within different school levels (i.e., primary school and secondary school) and on different day types (i.e., weekdays and weekend days) among youths with autism spectrum disorder (ASD). The sample was recruited from one city in Taiwan. A total of 68 male youths with ASD, aged 6-17 years, participated in the study. PA was assessed using an ActiGraph accelerometer, and sedentary behaviors (i.e., TV viewing, computer use, and reading time) were determined using a self-report log. The main findings were that (a) primary school youths with ASD were more active than secondary school youths with ASD on both weekdays and weekend days, but primary school youths with ASD also had more sedentary time than did secondary school youths with ASD on both weekdays and weekend days ; (b) secondary school youths with ASD were more active but also more sedentary on weekdays compared with weekend days, but they had more screen use on weekend days compared with on weekdays. Future interventions are required to decrease sedentary behavior and increase PA to improve the health of these youths according to school level and day of the week.

Lien vers le texte intégral (Open Access ou abonnement)

15. Rucińska Z, Fondelli T, Gallagher S. Embodied Imagination and Metaphor Use in Autism Spectrum Disorder. Healthcare (Basel, Switzerland). 2021 ; 9(2).

This paper discusses different frameworks for understanding imagination and metaphor in the context of research on the imaginative skills of children with autism spectrum disorder (ASD). In contrast to a standard linguistic framework, it advances an embodied and enactive account of imagination and metaphor. The paper describes a case study from a systemic therapeutic session with a child with ASD that makes use of metaphors. It concludes by outlining some theoretical insights into the imaginative skills of children with ASD that follow from taking the embodied-enactive perspective and proposes suggestions for interactive interventions to further enhance imaginative skills and metaphor understanding in children with ASD.

Lien vers le texte intégral (Open Access ou abonnement)

16. Salgado-Cacho JM, Moreno-Jiménez MDP, de Diego-Otero Y. Detection of Early Warning Signs in Autism Spectrum Disorders : A Systematic Review. Children (Basel, Switzerland). 2021 ; 8(2).

Due to the exponential increase of autism spectrum disorders’ prevalence in Western countries, it is necessary to improve early detection and intervention to enhance developmental milestones. This systematic review identified the most effective screening instrument, which can be used at an early age and which identifies the maximum number of autism cases. We identified several instruments with adequate predictive properties-the Autism Parent Screen for Infants (APSI), Battelle Development Inventory, second edition (BDI-2) ; Brief Infant-Toddler Social and Emotional Assessment (BITSEA) ; First Year Inventory (FYI) ; Infant-Toddler Checklist/Communication and Symbolic Behavior Scales Developmental Profile (ITC/CSBS-DP) ; Program of Research and Studies on AUTISM (PREAUT-Grid) ; Checklist for Early Signs of Developmental Disorders (CESDD) ; Social Attention and Communication Study (SACS) ; and the Screening Tool for Autism in Toddlers and Young Children (STAT)-that can be applied from 12 months of age in Western countries. The ITC/CSBS-DP has been proposed for universal screening from 12 months of age onwards, complemented by the Modified Checklist for Autism in Toddlers, Revised/Revised with Follow-Up (M-CHAT-R/F), which can be used from 15 months of age onwards. This strategy could improve early detection in at-risk children within the current health system, thus allowing for early intervention.

Lien vers le texte intégral (Open Access ou abonnement)

17. Siper PM, Layton C, Levy T, Lurie S, Benrey N, Zweifach J, Rowe M, Tang L, Guillory S, Halpern D, Giserman-Kiss I, Del Pilar Trelles M, Foss-Feig JH, De Rubeis S, Tavassoli T, Buxbaum JD, Kolevzon A. Sensory Reactivity Symptoms Are a Core Feature of ADNP Syndrome Irrespective of Autism Diagnosis. Genes. 2021 ; 12(3).

Background : Activity dependent neuroprotective protein (ADNP) syndrome is one of the most common single-gene causes of autism spectrum disorder (ASD) and intellectual disability, however, the phenotypes remain poorly described. Here we examine the sensory reactivity phenotype in children and adolescents with ADNP syndrome. Methods : Twenty-two individuals with ADNP syndrome received comprehensive clinical evaluations including standardized observations, caregiver interviews, and questionnaires to assess sensory reactivity symptoms. Relationships between sensory symptoms and age, sex, ASD, IQ, and adaptive behavior were examined. Genotype-phenotype correlations with the recurrent p.Tyr719* variant were also explored. Results : Sensory reactivity symptoms were observed and reported in all participants. A syndrome-specific phenotype was identified, characterized by high levels of sensory seeking across tactile, auditory, and visual domains. Tactile hyporeactivity, characterized by pain insensitivity, was reported in the majority of participants. Sensory symptoms were identified across individuals regardless of age, sex, IQ, adaptive ability, genetic variant, and most importantly, ASD status. No significant differences were identified between participants with and without the recurrent p.Tyr719* variant on any sensory measure. Conclusions : Sensory reactivity symptoms are a common clinical feature of ADNP syndrome. Quantifying sensory reactivity using existing standardized measures will enhance understanding of sensory reactivity in individuals with ADNP syndrome and will aid in clinical care. The sensory domain may also represent a promising target for treatment in clinical trials.

Lien vers le texte intégral (Open Access ou abonnement)

18. Smedler E, Kleppe J, Neufeld J, Lundin K, Bölte S, Landén M. Cerebrospinal fluid and serum protein markers in autism : a co-twin study. Journal of neurochemistry. 2021.

No robust biomarkers have yet been identified for autism spectrum disorder (ASD) or autistic traits. Familial factors likely influence biomarkers such as protein concentrations. Comparing twins with ASD or high autistic traits to the less affected co-twin allows estimating the impact of familial confounding. We measured 203 proteins in cerebrospinal fluid (n=86) and serum (n=127) in twins (mean age 14.2 years, 44.9% females) enriched for ASD and other neurodevelopmental conditions. Autistic traits were assessed by using the parent-report version of the Social Responsiveness Scale-2. In cerebrospinal fluid, autistic traits correlated negatively with three proteins and positively with one. In serum, autistic traits correlated positively with 15 and negatively with one. Also in serum, six were positively – and one negatively – associated with ASD. A pathway analysis of these proteins revealed immune system enrichment. In within twin pair analyses, autistic traits were associated with serum B-cell activating factor (BAFF) only, whereas Cystatin B (CSTB) remained significantly associated with ASD. These associations remained significant when only considering monozygotic twins. For the remainder, the within-pair analysis indicated familial confounding, including shared environment and genes, influencing both autism and protein levels. Our findings indicate proteins involved in immunity as putative biomarkers of autistic traits and ASD with partial genetic confounding. Although some results are in line with previous studies in general, further studies are needed for replication.

Lien vers le texte intégral (Open Access ou abonnement)

19. Temelturk RD, Yurumez E, Cıkılı Uytun M, Oztop DB. Parent-child interaction, parental attachment styles and parental alexithymia levels of children with ASD. Res Dev Disabil. 2021 ; 112 : 103922.

AIM : Given the recent findings regarding the increased evidence for the presence of the alexithymia in parents of children with autism spectrum disorder (ASD), the construct of alexithymia in parents of children with ASD and its effect on adult romantic attachment style of parents, family functioning and parent-child relationship were investigated. METHODS : The sample included children diagnosed as having ASD, developmental delay (DD), and 27 typically developing children aged 1-5 years and their parents. The Crowell procedure, an observational and structured assessment was performed, and the quality of the parent-child relationship was assessed using the Parent-Infant Relationship-Global Assessment Scale (PIR-GAS) based on DC : 0-5. The Toronto Alexithymia Scale-20, Experiences in Close Relationships Revised, and the Family Assessment Device were administered to the parents. RESULTS : PIR-GAS scores were lower in the ASD group compared with the scores of the other groups. Family functioning rated by fathers of children with DD was lower than in the other groups. However, there was no significant difference between the groups in terms of alexithymia levels, and parent’s own attachment styles in romantic relationships. CONCLUSIONS : ASD was found to be an independent predictor for disordered relationship between children and their parents. Appropriate family interventions focusing on enhancing social interaction and emotional development may be beneficial in the treatment of ASD.

Lien vers le texte intégral (Open Access ou abonnement)

20. Tiwari A, Khera R, Rahi S, Mehan S, Makeen HA, Khormi YH, Rehman MU, Khan A. Neuroprotective Effect of α-Mangostin in the Ameliorating Propionic Acid-Induced Experimental Model of Autism in Wistar Rats. Brain Sci. 2021 ; 11(3).

Several studies have documented the role of hyper-activation of extracellular signal-regulated kinases (ERK) in Autism pathogenesis. Alpha-mangostin (AMG) is a phytoconstituents with anti-oxidants, anti-inflammatory, and ERK inhibition properties in many diseases. Our research aims to investigate the neuroprotective effect of AMG in the rat model of intracerebroventricular-propionic acid (ICV-PPA) induced autism with a confirmation of its effect on the ERK signaling. Autism was induced in Wistar rats (total 36 rats ; 18 male/18 female) by multiple doses of PPA through ICV injection for 11 days. Actophotometer and beam walking tasks were used to evaluate animals’ motor abilities, and the Morris water maze task was utilized to confirm the cognition and memory in animals. Long term administration of AMG 100 mg/kg and AMG 200mg/kg continued from day 12 to day 44 of the experiment. Before that, animals were sacrificed, brains isolated, morphological, gross pathological studies were performed, and neurochemical analysis was performed in the brain homogenates. Cellular and molecular markers, including ERK, myelin basic protein, apoptotic markers including caspase-3, Bax, Bcl-2, neuroinflammatory markers, neurotransmitters, and oxidative stress markers, have been tested throughout the brain. Thus, AMG reduces the overactivation of the ERK signaling and also restored autism-like behavioral and neurochemical alterations.

Lien vers le texte intégral (Open Access ou abonnement)

21. Traetta ME, Codagnone MG, Uccelli NA, Ramos AJ, Zárate S, Reinés A. Hippocampal neurons isolated from rats subjected to the valproic acid model mimic in vivo synaptic pattern : evidence of neuronal priming during early development in autism spectrum disorders. Mol Autism. 2021 ; 12(1) : 23.

BACKGROUND : Autism spectrum disorders (ASD) are synaptopathies characterized by area-specific synaptic alterations and neuroinflammation. Structural and adhesive features of hippocampal synapses have been described in the valproic acid (VPA) model. However, neuronal and microglial contribution to hippocampal synaptic pattern and its time-course of appearance is still unknown. METHODS : Male pups born from pregnant rats injected at embryonic day 10.5 with VPA (450 mg/kg, i.p.) or saline (control) were used. Maturation, exploratory activity and social interaction were assessed as autistic-like traits. Synaptic, cell adhesion and microglial markers were evaluated in the CA3 hippocampal region at postnatal day (PND) 3 and 35. Primary cultures of hippocampal neurons from control and VPA animals were used to study synaptic features and glutamate-induced structural remodeling. Basal and stimuli-mediated reactivity was assessed on microglia primary cultures isolated from control and VPA animals. RESULTS : At PND3, before VPA behavioral deficits were evident, synaptophysin immunoreactivity and the balance between the neuronal cell adhesion molecule (NCAM) and its polysialylated form (PSA-NCAM) were preserved in the hippocampus of VPA animals along with the absence of microgliosis. At PND35, concomitantly with the establishment of behavioral deficits, the hippocampus of VPA rats showed fewer excitatory synapses and increased NCAM/PSA-NCAM balance without microgliosis. Hippocampal neurons from VPA animals in culture exhibited a preserved synaptic puncta number at the beginning of the synaptogenic period in vitro but showed fewer excitatory synapses as well as increased NCAM/PSA-NCAM balance and resistance to glutamate-induced structural synaptic remodeling after active synaptogenesis. Microglial cells isolated from VPA animals and cultured in the absence of neurons showed similar basal and stimuli-induced reactivity to the control group. Results indicate that in the absence of glia, hippocampal neurons from VPA animals mirrored the in vivo synaptic pattern and suggest that while neurons are primed during the prenatal period, hippocampal microglia are not intrinsically altered. CONCLUSIONS : Our study suggests microglial role is not determinant for developing neuronal alterations or counteracting neuronal outcome in the hippocampus and highlights the crucial role of hippocampal neurons and structural plasticity in the establishment of the synaptic alterations in the VPA rat model.

Lien vers le texte intégral (Open Access ou abonnement)

22. Villa C, Combi R, Conconi D, Lavitrano M. Patient-Derived Induced Pluripotent Stem Cells (iPSCs) and Cerebral Organoids for Drug Screening and Development in Autism Spectrum Disorder : Opportunities and Challenges. Pharmaceutics. 2021 ; 13(2).

Autism spectrum disorder (ASD) represents a group of neurodevelopmental diseases characterized by persistent deficits in social communication, interaction, and repetitive patterns of behaviors, interests, and activities. The etiopathogenesis is multifactorial with complex interactions between genetic and environmental factors. The clinical heterogeneity and complex etiology of this pediatric disorder have limited the development of pharmacological therapies. The major limit to ASD research remains a lack of relevant human disease models which can faithfully recapitulate key features of the human pathology and represent its genetic heterogeneity. Recent advances in induced pluripotent stem cells (iPSCs), reprogrammed from somatic cells of patients into all types of patient-specific neural cells, have provided a promising cellular tool for disease modeling and development of novel drug treatments. The iPSCs technology allowed not only a better investigation of the disease etiopathogenesis but also opened up the potential for personalized therapies and offered new opportunities for drug discovery, pharmacological screening, and toxicity assessment. Moreover, iPSCs can be differentiated and organized into three-dimensional (3D) organoids, providing a model which mimics the complexity of the brain’s architecture and more accurately recapitulates tissue- and organ-level disease pathophysiology. The aims of this review were to describe the current state of the art of the use of human patient-derived iPSCs and brain organoids in modeling ASD and developing novel therapeutic strategies and to discuss the opportunities and major challenges in this rapidly moving field.

Lien vers le texte intégral (Open Access ou abonnement)