Pubmed du 24/05/20

dimanche 24 mai 2020

1. Ben Jdila M, Charfi Triki C, Ghorbel R, Bouchalla W, Ben Ncir S, Kamoun F, Fakhfakh F. Unusual double mutation in MECP2and CDKL5 genes in Rett-like Syndrome : correlation with phenotype and genes expression. Clin Chim Acta. 2020.

INTRODUCTION : Rett syndrome (RTT) is a neuro-developmental disorder affecting almost exclusively females and it divided into classical and atypical forms of the disease. RTT-like syndrome was also described and presents an overlapping phenotype of RTT. RTT-like syndrome has been associated with several genes including MECP2 and CDKL5 having common biological pathways and regulatory interactions especially during neural maturation and synaptogenesis. METHODS : We report patient with Rett-like syndrome for whom clinical features and their progression guided toward the screening of two candidate genes MECP2 and CDKL5 by sequencing. Severity score was evaluated by "Rett Assessment Rating Scale" (R.A.R.S.). Predictions of pahogenicity and functional effects used several bioinformatic tools and qRT-PCR was conducted to evaluate gene expression. RESULTS : Mutational screening revealed two mutations c.1065 C>A (p.S355R) in MECP2 gene and c.616 G>A (p.D206N) mutation in CDKL5 gene in the patient with a high R.A.R.S. Bioinformatic investigations predicted a moderate effect of p.S355R in MECP2 gene but a more pathogenic one of p.D206N mutation in CDKL5. Effect of c.616 G>A mutation on structure and stability of CDKL5 mRNA was confirmed by qRT-PCR. Additionally, analysis of gene expression revealed a drastic effect of CDKL5 mutant on its MeCP2 and Dnmt1 substrates and also on its MYCN regulator. CONCLUSIONS : The co-existence of the two mutations in CDKL5 and MECP2 genes could explain the severe phenotype in our patient with RTT-Like and is consistent with the data related to the interactions of CDKL5 with MeCP2 and Dnmt1 proteins.

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2. Cicaloni V, Pecorelli A, Tinti L, Rossi M, Benedusi M, Cervellati C, Spiga O, Santucci A, Hayek J, Salvini L, Tinti C, Valacchi G. Proteomic profiling reveals mitochondrial alterations in Rett syndrome. Free radical biology & medicine. 2020.

Rett syndrome (RTT) is a pervasive neurodevelopmental disorder associated with mutation in MECP2 gene. Despite a well-defined genetic cause, there is a growing consensus that a metabolic component could play a pivotal role in RTT pathophysiology. Indeed, perturbed redox homeostasis and inflammation, i.e. oxinflammation, with mitochondria dysfunction as the central hub between the two phenomena, appear as possible key contributing factors to RTT pathogenesis and its clinical features. While these RTT-related changes have been widely documented by transcriptomic profiling, proteomics studies supporting these evidences are still limited. Here, using primary dermal fibroblasts from control and patients, we perform a large-scale proteomic analysis that, together with data mining approaches, allow us to carry out the first comprehensive characterization of RTT cellular proteome, showing mainly changes in expression of proteins involved in the mitochondrial network. These findings parallel with an altered expression of key mediators of mitochondrial dynamics and mitophagy associated with abnormal mitochondrial morphology. In conclusion, our proteomic analysis confirms the pathological relevance of mitochondrial dysfunction in RTT pathogenesis and progression.

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3. Cooke E, Smith V, Brenner M. Parents’ experiences of accessing respite care for children with Autism Spectrum Disorder (ASD) at the acute and primary care interface : a systematic review. BMC pediatrics. 2020 ; 20(1) : 244.

BACKGROUND : Population prevalence estimates by the World Health Organisation suggest that 1 in 160 children worldwide has an Autism Spectrum Disorder (ASD). Accessing respite care services for children with an ASD can often be a daunting and exhaustive process, with parents sometimes forced to access acute hospital services as an initial point of contact for respite care or in a crisis situation. To gain an in-depth understanding of accessing respite care for children with an ASD, from the perspectives of parents, a systematic review of the evidence on parent’s experiences and views of respite care for children with an ASD at the acute and primary interface was undertaken. METHODS : Pubmed, Embase, CINAHL and PsycINFO were systematically searched. Studies identified as relevant based on predetermined eligibility criteria were selected for inclusion. The search strategy also targeted unpublished studies and grey literature. Qualitative data and qualitative components of mixed method studies that represented the experiences of parents accessing respite care for children with an ASD were eligible for inclusion. A meta-aggregative approach was used during data synthesis. RESULTS : Database searching elicited 430 records of which 291 studies remained after removal of duplicates. These 291 studies were screened for title and abstract by two reviewers resulting in 31 studies to be screened at full text and assessed for eligibility. Six studies met the inclusion criteria and a further additional study also met the inclusion criteria during a manual search. As a result, 7 studies were selected for the review as set out in Fig. 1. CONCLUSION : In the absence of appropriate services and defined pathways to support services such as respite care, overwhelmed parents and community providers of mental health resources may not be in a position to meet the specific needs of children with an ASD and their families which may be contributing to a direct increase in hospitalizations. This systematic review identified a number of barriers to respite care, of which the findings can be used to inform future service development and further research. Knowledge of parental experiences in caring for a child with an ASD is vital in addressing the need and type of respite care required for children with an ASD. SYSTEMATIC REVIEW REGISTRATION : PROSPERO CRD42018106629.

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4. Crucitti J, Hyde C, Enticott PG, Stokes MA. Are Vermal Lobules VI-VII Smaller in Autism Spectrum Disorder ?. Cerebellum (London, England). 2020.

Cerebellar volume, in particular vermal lobule areas VI-VII, have been extensively researched in individuals with autism spectrum disorder (ASD), although findings are often unclear. The aim of the present study is to consolidate all existing cerebellar and age data of individuals with ASD, and compare this data to typically developing (TD) controls. Raw data, or the means and standard deviations of cerebellar volume and age, were obtained from 17 studies (N(Cerebellum) : 421 ASD and 370 TD participants ; N(VI-VII) : 506 ASD and 290 TD participants). Total cerebellar volume, or VI-VII area, was plotted against age and lines of fit of ASD and TD data were compared. Mean differences in cerebellar volume and VI-VII area between participants with ASD and TD participants were then compared via ANCOVA analyses. Findings revealed multiple differences in VI-VII area between participants with ASD and TD participants below 18 years of age. Additionally, cerebellar volume was greater in males with ASD than TD males between 2 and 4 years. In the present study, cerebellar volume and VI-VII area show different rates of change across age for those with autism compared with those without. These morphological differences provide a neurobiological justification to investigate related behavioural correlates.

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5. Dawson G, Sun JM, Baker J, Carpenter K, Compton S, Deaver M, Franz L, Heilbron N, Herold B, Horrigan J, Howard J, Kosinski A, Major S, Murias M, Page K, Prasad VK, Sabatos-DeVito M, Sanfilippo F, Sikich L, Simmons R, Song A, Vermeer S, Waters-Pick B, Troy J, Kurtzberg J. A Phase II Randomized Clinical Trial of the Safety and Efficacy of Intravenous Umbilical Cord Blood Infusion for Treatment of Children with Autism Spectrum Disorder. The Journal of pediatrics. 2020.

OBJECTIVE : To evaluate whether umbilical cord blood (CB) infusion is safe and associated with improved social and communication abilities in children with autism spectrum disorder (ASD). STUDY DESIGN : This prospective, randomized, placebo-controlled, double-blind study included 180 children with ASD, aged 2-7 years, who received a single intravenous autologous (n = 56) or allogeneic (n = 63) CB infusion vs placebo (n = 61) and were evaluated at 6 months postinfusion. RESULTS : CB infusion was safe and well tolerated. Analysis of the entire sample showed no evidence that CB was associated with improvements in the primary outcome, social communication (Vineland Adaptive Behavior Scales-3 [VABS-3] Socialization Domain), or the secondary outcomes, autism symptoms (Pervasive Developmental Disorder Behavior Inventory) and vocabulary (Expressive One-Word Picture Vocabulary Test). There was also no overall evidence of differential effects by type of CB infused. In a subanalysis of children without intellectual disability (ID), allogeneic, but not autologous, CB was associated with improvement in a larger percentage of children on the clinician-rated Clinical Global Impression-Improvement scale, but the OR for improvement was not significant. Children without ID treated with CB showed significant improvements in communication skills (VABS-3 Communication Domain), and exploratory measures including attention to toys and sustained attention (eye-tracking) and increased alpha and beta electroencephalographic power. CONCLUSIONS : Overall, a single infusion of CB was not associated with improved socialization skills or reduced autism symptoms. More research is warranted to determine whether CB infusion is an effective treatment for some children with ASD.

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6. Eshraghi AA, Li C, Alessandri M, Messinger DS, Eshraghi RS, Mittal R, Armstrong FD. COVID-19 : overcoming the challenges faced by individuals with autism and their families. Lancet Psychiatry. 2020 ; 7(6) : 481-3.

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7. Frasch MG, Shen C, Wu HT, Mueller A, Neuhaus E, Bernier RA, Kamara D, Beauchaine TP. Brief Report : Can a Composite Heart Rate Variability Biomarker Shed New Insights About Autism Spectrum Disorder in School-Aged Children ?. J Autism Dev Disord. 2020.

Several studies show altered heart rate variability (HRV) in autism spectrum disorder (ASD), but findings are neither universal nor specific to ASD. We apply a set of linear and nonlinear HRV measures-including phase rectified signal averaging-to segments of resting ECG data collected from school-age children with ASD, age-matched typically developing controls, and children with other psychiatric conditions characterized by altered HRV (conduct disorder, depression). We use machine learning to identify time, frequency, and geometric signal-analytical domains that are specific to ASD (receiver operating curve area = 0.89). This is the first study to differentiate children with ASD from other disorders characterized by altered HRV. Despite a small cohort and lack of external validation, results warrant larger prospective studies.

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8. Gąssowska-Dobrowolska M, Cieślik M, Czapski GA, Jęśko H, Frontczak-Baniewicz M, Gewartowska M, Dominiak A, Polowy R, Filipkowski RK, Babiec L, Adamczyk A. Prenatal Exposure to Valproic Acid Affects Microglia and Synaptic Ultrastructure in a Brain-Region-Specific Manner in Young-Adult Male Rats : Relevance to Autism Spectrum Disorders. International journal of molecular sciences. 2020 ; 21(10).

Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental conditions categorized as synaptopathies. Environmental risk factors contribute to ASD aetiology. In particular, prenatal exposure to the anti-epileptic drug valproic acid (VPA) may increase the risk of autism. In the present study, we investigated the effect of prenatal exposure to VPA on the synaptic morphology and expression of key synaptic proteins in the hippocampus and cerebral cortex of young-adult male offspring. To characterize the VPA-induced autism model, behavioural outcomes, microglia-related neuroinflammation, and oxidative stress were analysed. Our data showed that prenatal exposure to VPA impaired communication in neonatal rats, reduced their exploratory activity, and led to anxiety-like and repetitive behaviours in the young-adult animals. VPA-induced pathological alterations in the ultrastructures of synapses accompanied by deregulation of key pre- and postsynaptic structural and functional proteins. Moreover, VPA exposure altered the redox status and expression of proinflammatory genes in a brain region-specific manner. The disruption of synaptic structure and plasticity may be the primary insult responsible for autism-related behaviour in the offspring. The vulnerability of specific synaptic proteins to the epigenetic effects of VPA may highlight the potential mechanisms by which prenatal VPA exposure generates behavioural changes.

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9. Gulisano M, Barone R, Alaimo S, Ferro A, Pulvirenti A, Cirnigliaro L, Di Silvestre S, Martellino S, Maugeri N, Milana MC, Scerbo M, Rizzo R. Disentangling Restrictive and Repetitive Behaviors and Social Impairments in Children and Adolescents with Gilles de la Tourette Syndrome and Autism Spectrum Disorder. Brain Sci. 2020 ; 10(5).

Gilles de la Tourette syndrome (GTS) and autism spectrum disorder (ASD) are two neurodevelopmental disorders with male predominance, frequently comorbid, that share clinical and behavioral features. The incidence of ASD in patients affected by GTS was reported to be between 2.9% and 22.8%. We hypothesized that higher ASD rates among children affected by GTS previously reported may be due to difficulty in discriminating GTS sub-phenotypes from ASD, and the higher scores in the restrictive and repetitive behaviors in particular may represent at least a "false comorbidity". We studied a large population of 720 children and adolescents affected by GTS (n = 400) and ASD (n = 320), recruited from a single center. Patients were all assessed with The Yale Global Tic Severity Rating Scale (YGTSS), The Autism Diagnostic Observation Schedule (ADOS), The Autism Diagnostic Interview Revised (ADI-R), The Children’s Yale-Brown Obsessive-Compulsive Scale (CY-BOCS), and The Children’s Yale-Brown Obsessive-Compulsive Scale for autism spectrum disorder (CY-BOCS ASD). Our results showed statistically significant differences in ADOS scores for social aspects between GTS with comorbid attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD) sub-phenotypes and ASD. No differences were present when we compared GTS with comorbid ASD sub-phenotype to ASD, while repetitive and restrictive behavior scores in ASD did not present statistical differences in the comparison with GTS and comorbid OCD and ASD sub-phenotypes. We also showed that CY-BOCS ASD could be a useful instrument to correctly identify OCD from ASD symptoms.

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10. Hillier A, Buckingham A, Schena D, 2nd. Physical Activity Among Adults With Autism : Participation, Attitudes, and Barriers. Perceptual and motor skills. 2020 : 31512520927560.

Children and adolescents with autism spectrum disorder (ASD) have shown have low levels of physical fitness, increasing risks for health-related problems associated with inactivity, such as being overweight, when compared with typically developing children. Few studies have examined physical activity (PA) among adults with ASD. This U.S.-based study examined participation in and attitudes and barriers toward PA among adults with ASD and their peers without ASD. We used standardized existing scales to survey participants for data regarding their frequency of engagement in weekly PA (strenuous, moderate, light), attitudes toward PA, expectations of others, perceived behavioral control, intention toward PA, and perceived PA barriers. Findings indicated that, on average, the ASD group compared with the comparison group reported (a) less frequent strenuous or moderate PA, (b) less positive attitudes toward PA, (c) less perceived behavioral control or ease of performing PA, and (d) more PA barriers. There was also evidence that the ASD group reported less PA intent, but there was no difference between groups regarding beliefs about others’ PA expectations for them. These findings suggest a need for more PA for adults with ASD, particularly because PA has potential to attenuate such ASD challenges as anxiety, stress, and sleeping difficulties.

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11. Kabitzke P, Morales D, He D, Cox K, Sutphen J, Thiede L, Sabath E, Hanania T, Biemans B, Brunner D. Mouse Model Systems of Autism Spectrum Disorder : Replicability and Informatics Signature. Genes, brain, and behavior. 2020 : e12676.

Phenotyping mouse model systems of human disease has proven to be a difficult task, with frequent poor inter- and intra-laboratory replicability, particularly in behavioral domains such as social and cognitive function. However, establishing robust animal model systems with strong construct validity is of fundamental importance as they are central tools for understanding disease pathophysiology and developing therapeutics. To complete our studies of mouse model systems relevant to autism spectrum disorder (ASD), we present a replication of the main findings from our two published studies of five genetic mouse model systems of ASD. To assess the intra-laboratory robustness of previous results, we chose the two model systems that showed the greatest phenotypic differences, the Shank3/F and Cntnap2, and repeated assessments of general health, activity, and social behavior. We additionally explored all five model systems in the same framework, comparing all results obtained in this three-yearlong effort using informatics techniques to assess commonalities and differences. Our results showed high intra-laboratory replicability of results, even for those with effect sizes that were not particularly large, suggesting that discrepancies in the literature may be dependent on subtle but pivotal differences in testing conditions, housing enrichment, or background strains and less so on the variability of the behavioral phenotypes. The overall informatics analysis suggests that in our behavioral assays we can separate the set of tested mouse model system into two main classes that in some aspects lie on opposite ends of the behavioral spectrum, supporting the view that autism is not a unitary concept.

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12. Kodak T, Bergmann S. Autism Spectrum Disorder : Characteristics, Associated Behaviors, and Early Intervention. Pediatr Clin North Am. 2020 ; 67(3) : 525-35.

Autism spectrum disorder (ASD) is characterized by deficits in social communication and interaction and the presence of restricted and repetitive patterns of behavior and interests. Currently, ASD affects 1 in 59 individuals and can be a costly disorder across one’s lifetime. Because of the prevalence, costs, and range of behavioral needs, early intervention is vital to teach skills across a variety of domains and prevent the development or exacerbation of behavioral deficits and excesses. Interventions based on applied behavior analysis have the most empirical support ; several strategies to teach social skills, communication, and adaptive skills are discussed.

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13. Kurtz PF, Leoni M, Hagopian LP. Behavioral Approaches to Assessment and Early Intervention for Severe Problem Behavior in Intellectual and Developmental Disabilities. Pediatr Clin North Am. 2020 ; 67(3) : 499-511.

This article summarizes the literature on prevalence and establishment of severe problem behavior in individuals with intellectual and developmental disabilities, empirical support for applied behavior analysis, and evidence-based behavioral assessment and treatment procedures. Early intervention and prevention approaches and the role of the pediatrician with regard to surveillance, early intervention, and coordination of care are discussed.

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14. Nadeem R, Hussain T, Sajid H. C reactive protein elevation among children or among mothers’ of children with autism during pregnancy, a review and meta-analysis. BMC Psychiatry. 2020 ; 20(1) : 251.

OBJECTIVE : To evaluate if children with ASD, or mothers of ASD children have elevated CRP during pregnancy. BACKGROUND : Autism spectrum disorder (ASD) is a neuro developmental disorder with incidence of 1 in 68 children occur in all racial, ethnic, and socioeconomic groups. Economic burden between $11.5 billion - $60.9 billion and family average medical expenditures of $4110-$6200 per year. Conflicting evidence exist about role of maternal CRP during pregnancy with ASD child. METHODS : Searches on database ; Pubmed, Medline, Embase and google scholar using key words ; C reactive protein (CRP), Maternal CRP, ASD, autism, autistic disorder, Inflammation. All English-language studies published between 1960 and 2019 pertaining to CRP and ASD. All Studies which provided data on CRP levels during pregnancy (mCRP) of Mothers of offsprings with ASD and (mCRP) of mothers of normal subjects were selected. Data were extracted in the form of odd ratios of having high mCRP in mothers of children with ASD versus mCRP of mothers of normal controls. Since these odd ratios were adjusted, therefore no Meta regression were attempted. Significant heterogeneity was found ; therefore, random effect model was employed. RESULTS : Review of CRP levels in children with ASD showed higher level in children with ASD than control, although different methodology and absence of numerical data did not allow metanalysis. Regarding mCRP and ASD, three studies were identified that provide data on mCRP and ASD. Four datasets were created from these 3 studies as the study by Zerbo et al. provided data in 2 subsets. Total number of subjects were 5258 (Brown, N = 677, Zerbo = 416, Koks = 4165) extracted data from these studies was pooled for analysis. Random effect model was employed and substantial heterogeneity among the studies was observed 11. Mothers of children with ASD have adjusted Odd ratio of 1.02 (0.948 to 1.103, I2 = 75, P = 0.558) to have high mCRP comparing mothers of control. CONCLUSION : Mothers of children with ASD appear not to have elevated CRP during pregnancy. Children with ASD appear to have higher levels of CRP levels.

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15. Naoko D, Takashi A, Tomoko O. Development and Preliminary Validation of the Couples’ Stigma Scale to Assess Self-Stigma among the Partners of Persons with Autism Spectrum Disorder in Japan. Int J Environ Res Public Health. 2020 ; 17(10).

Spouses of individuals with autism spectrum disorder (ASD) may struggle with self-stigma and may require attention and care ; however, no scale exists to measure the stigma of spouses of persons with ASD. This study created and investigated the construct validity of the Couples Stigma Scale. This scale consists of 14 items and it was designed based on prior literature, interviews, and the self-stigma theory to assess the self-stigma experienced by spouses of people with ASD. A survey was conducted with spouses of persons with ASD who participated in a self-help group. Responses were obtained from 259 people, of which 253 women were included in the analysis. Exploratory factor analysis was performed separately with two independent groups, indicating a four-factor structure, to determine structural validity. The factor loadings of the items constituting the four factors were 0.39 or greater. Regarding external validity, the correlation coefficient between the Couples Stigma Scale and the World Health Organization Quality of Life (WHOQOL) score was -0.341 (p < 0.001), and the domain correlation coefficient was significant for all relevant WHOQOL domains. Our results suggest that the Japanese version of the Couples Stigma Scale is a valid instrument for assessing self-stigma in the spouses of persons with ASD.

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16. Price J. Cell therapy approaches to autism : a review of clinical trial data. Mol Autism. 2020 ; 11(1) : 37.

A number of clinical trials of cell therapies for autism spectrum disorder have been conducted, and some have published their outcomes. This review considers the data that have emerged from this small set of published trials, evaluates their success, and proposes further steps that could be taken if this field of endeavour is to be pursued further. A number of reservations arise from this tranche of studies, specifically the absence of identified therapeutic targets, and deficiencies in the therapeutic approach that is being employed. If this therapeutic direction is to be pursued further, then additional pre-clinical studies are recommended that might lead to improvements in patient stratification, biomarkers, the defined mode of action, and the preparation and identification of the therapeutic cells themselves.

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17. Robea MA, Luca AC, Ciobica A. Relationship between Vitamin Deficiencies and Co-Occurring Symptoms in Autism Spectrum Disorder. Medicina (Kaunas, Lithuania). 2020 ; 56(5).

Recently, connections have been made between feeding and eating problems and autism spectrum disorder (ASD) and between autism pathophysiology and diet issues. These could explain some of the mechanisms which have not yet been discovered or are not sufficiently characterized. Moreover, there is an increased awareness for micronutrients in ASD due to the presence of gastrointestinal (GI) problems that can be related to feeding issues. For example, levels of vitamins B(1), B(6), B(12), A and D are often reported to be low in ASD children. Thus, in the present mini review we focused on describing the impact of some vitamins deficiencies and their relevance in ASD patients.

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18. Shuid AN, Jayusman PA, Shuid N, Ismail J, Kamal Nor N, Naina Mohamed I. Update on Atypicalities of Central Nervous System in Autism Spectrum Disorder. Brain Sci. 2020 ; 10(5).

Autism spectrum disorder (ASD) is a heterogeneous, behaviorally defined, neurodevelopmental disorder that has been modeled as a brain-based disease. The behavioral and cognitive features of ASD are associated with pervasive atypicalities in the central nervous system (CNS). To date, the exact mechanisms underlying the pathophysiology of ASD still remain unknown and there is currently no cure or effective treatment for this disorder. Many publications implicated the association of ASD with inflammation, immune dysregulation, neurotransmission dysfunction, mitochondrial impairment and cell signaling dysregulation. This review attempts to highlight evidence of the major pathophysiology of ASD including abnormalities in the brain structure and function, neuroglial activation and neuroinflammation, glutamatergic neurotransmission, mitochondrial dysfunction and mechanistic target of rapamycin (mTOR) signaling pathway dysregulation. Molecular and cellular factors that contributed to the pathogenesis of ASD and how they may affect the development and function of CNS are compiled in this review. However, findings of published studies have been complicated by the fact that autism is a very heterogeneous disorder ; hence, we addressed the limitations that led to discrepancies in the reported findings. This review emphasizes the need for future studies to control study variables such as sample size, gender, age range and intelligence quotient (IQ), all of which that could affect the study measurements. Neuroinflammation or immune dysregulation, microglial activation, genetically linked neurotransmission, mitochondrial dysfunctions and mTOR signaling pathway could be the primary targets for treating and preventing ASD. Further research is required to better understand the molecular causes and how they may contribute to the pathophysiology of ASD.

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19. Vigli D, Palombelli G, Fanelli S, Calamandrei G, Canese R, Mosca L, Luisa Scattoni M, Ricceri L. Maternal Immune Activation in mice only partially recapitulates the Autism Spectrum Disorders symptomatology. Neuroscience. 2020.

Prenatal viral/bacterial infections are considered risk factors for autism spectrum disorders (ASD) and rodent models of maternal immune activation (MIA) have been developed and extensively used in preclinical studies. Poly inosinic-cytidylic acid (Poly I:C) was injected in C57BL6/J dams to mimic a viral infection on gestational day 12.5 ; the experimental design includes 10/12 litters in each treatment group and data were analysed always considering the litter-effect ; neonatal (spontaneous motor behaviour and ultrasonic vocalizations) and adult [open field, marble burying, social approach, fear conditioning, prepulse inhibition (PPI)] offspring of both sexes were tested. In vivo magnetic resonance imaging/spectroscopy (MRI-MRS) and high-performance liquid chromatography (HPLC) to quantify both aminoacid and/or neurotransmitter concentration in cortical and striatal regions were also carried out. In both sexes high levels of repetitive motor responses and sensory gating deficits in PPI were the more striking effects of Poly I:C, whereas no alteration of social responses were evidenced. Poly I:C treatment did not affect mean values, but, intriguingly, increased variability in the levels of four aminoacids (aspartate glycine and GABA) selectively in males. As a whole prenatal Poly I:C induced relevant long-term alterations in explorative-stereotyped motor responses and in sensory gating, sparing cognitive and social competences. When systematically assessing differences between male and female siblings within each litter, no significant sex differences were evident except for increased variability of four aminoacid levels in male brains. As a whole, prenatal Poly I:C paradigms appear to be a useful tool to investigate the profound and translationally-relevant effects of developmental immune activation on brain and behavioural development, not necessarily recapitulating the full ASD symptomatology.

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