Pubmed du 09/04/23
1. Cao X, Tang X, Feng C, Lin J, Zhang H, Liu Q, Zheng Q, Zhuang H, Liu X, Li H, Khan NU, Shen L. A Systematic Investigation of Complement and Coagulation-Related Protein in Autism Spectrum Disorder Using Multiple Reaction Monitoring Technology. Neuroscience bulletin. 2023.
Autism spectrum disorder (ASD) is one of the common neurodevelopmental disorders in children. Its etiology and pathogenesis are poorly understood. Previous studies have suggested potential changes in the complement and coagulation pathways in individuals with ASD. In this study, using multiple reactions monitoring proteomic technology, 16 of the 33 proteins involved in this pathway were identified as differentially-expressed proteins in plasma between children with ASD and controls. Among them, CFHR3, C4BPB, C4BPA, CFH, C9, SERPIND1, C8A, F9, and F11 were found to be altered in the plasma of children with ASD for the first time. SERPIND1 expression was positively correlated with the CARS score. Using the machine learning method, we obtained a panel composed of 12 differentially-expressed proteins with diagnostic potential for ASD. We also reviewed the proteins changed in this pathway in the brain and blood of patients with ASD. The complement and coagulation pathways may be activated in the peripheral blood of children with ASD and play a key role in the pathogenesis of ASD.
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2. Farzan M, Farzan M, Amini-Khoei H, Shahrani M, Bijad E, Anjomshoa M, Shabani S. Protective effects of vanillic acid on autistic-like behaviors in a rat model of maternal separation stress: Behavioral, electrophysiological, molecular and histopathological alterations. International immunopharmacology. 2023; 118: 110112.
Compounds derived from herbs exhibit a range of biological properties, including anti-inflammatory, antioxidant, and neuroprotective properties. However, the exact mechanism of action of these compounds in various neurological disorders is not fully discovered yet. Herein, the present work detected the effect of Vanillic acid (VA), a widely-used flavoring agent derived from vanillin, on autistic-like behaviors to assess the probable underlying mechanisms that mediate behavioral, electrophysiological, molecular, and histopathological alterations in the rat model of maternal separation (MS) stress. Maternal separated rats were treated with VA (25, 50, and 100 mg/kg interperitoneally for 14 days). In addition, anxiety-like, autistic-like behaviors, and learning and memory impairment were evaluated using various behavioral tests. Hippocampus samples were assessed histopathologically by H&E staining. Levels of malondialdehyde (MDA) and antioxidant capacity (by the FRAP method), as well as nitrite levels, were measured in brain tissue. Moreover, gene expression of inflammatory markers (IL-1β, TLR-4, TNF-α, and NLRP3) was evaluated in the hippocampus. Electrophysiological alterations were also estimated in the hippocampus by long-term potentiation (LTP) assessments. Results showed that VA reversed the negative effects of MS on behavior. VA increased the diameter and decreased the percentage of dark neurons in the CA3 area. Accordingly, VA decreased MDA and nitrite levels and increased the antioxidant capacity in brain samples and decreased the expression of all inflammatory genes. VA treated rats showed significant improvements in all LTP parameters. This study provided evidence suggesting a possible role for VA in preventing autism spectrum disorder (ASD) by regulating immune signaling.
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3. Hudac CM, Friedman NR, Ward VR, Estreicher RE, Dorsey GC, Bernier RA, Kurtz-Nelson EC, Earl RK, Eichler EE, Neuhaus E. Characterizing Sensory Phenotypes of Subgroups with a Known Genetic Etiology Pertaining to Diagnoses of Autism Spectrum Disorder and Intellectual Disability. Journal of autism and developmental disorders. 2023: 1-16.
We aimed to identify unique constellations of sensory phenotypes for genetic etiologies associated with diagnoses of autism spectrum disorder (ASD) and intellectual disability (ID). Caregivers reported on sensory behaviors via the Sensory Profile for 290 participants (younger than 25 years of age) with ASD and/or ID diagnoses, of which ~ 70% have a known pathogenic genetic etiology. Caregivers endorsed poor registration (i.e., high sensory threshold, passive behaviors) for all genetic subgroups relative to an « idiopathic » comparison group with an ASD diagnosis and without a known genetic etiology. Genetic profiles indicated prominent sensory seeking in ADNP, CHD8, and DYRK1A, prominent sensory sensitivities in SCN2A, and fewer sensation avoidance behaviors in GRIN2B (relative to the idiopathic ASD comparison group).
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4. Molloy CJ, Quigley C, McNicholas Á, Lisanti L, Gallagher L. A review of the cognitive impact of neurodevelopmental and neuropsychiatric associated copy number variants. Translational psychiatry. 2023; 13(1): 116.
The heritability of intelligence or general cognitive ability is estimated at 41% and 66% in children and adults respectively. Many rare copy number variants are associated with neurodevelopmental and neuropsychiatric conditions (ND-CNV), including schizophrenia and autism spectrum disorders, and may contribute to the observed variability in cognitive ability. Here, we reviewed studies of intelligence quotient or cognitive function in ND-CNV carriers, from both general population and clinical cohorts, to understand the cognitive impact of ND-CNV in both contexts and identify potential genotype-specific cognitive phenotypes. We reviewed aggregate studies of sets ND-CNV broadly linked to neurodevelopmental and neuropsychiatric conditions, and genotype-first studies of a subset of 12 ND-CNV robustly associated with schizophrenia and autism. Cognitive impacts were observed across ND-CNV in both general population and clinical cohorts, with reports of phenotypic heterogeneity. Evidence for ND-CNV-specific impacts were limited by a small number of studies and samples sizes. A comprehensive understanding of the cognitive impact of ND-CNVs would be clinically informative and could identify potential educational needs for ND-CNV carriers. This could improve genetic counselling for families impacted by ND-CNV, and clinical outcomes for those with complex needs.
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5. Munz M, Bharioke A, Kosche G, Moreno-Juan V, Brignall A, Rodrigues TM, Graff-Meyer A, Ulmer T, Haeuselmann S, Pavlinic D, Ledergerber N, Gross-Scherf B, Rózsa B, Krol J, Picelli S, Cowan CS, Roska B. Pyramidal neurons form active, transient, multilayered circuits perturbed by autism-associated mutations at the inception of neocortex. Cell. 2023.
Cortical circuits are composed predominantly of pyramidal-to-pyramidal neuron connections, yet their assembly during embryonic development is not well understood. We show that mouse embryonic Rbp4-Cre cortical neurons, transcriptomically closest to layer 5 pyramidal neurons, display two phases of circuit assembly in vivo. At E14.5, they form a multi-layered circuit motif, composed of only embryonic near-projecting-type neurons. By E17.5, this transitions to a second motif involving all three embryonic types, analogous to the three adult layer 5 types. In vivo patch clamp recordings and two-photon calcium imaging of embryonic Rbp4-Cre neurons reveal active somas and neurites, tetrodotoxin-sensitive voltage-gated conductances, and functional glutamatergic synapses, from E14.5 onwards. Embryonic Rbp4-Cre neurons strongly express autism-associated genes and perturbing these genes interferes with the switch between the two motifs. Hence, pyramidal neurons form active, transient, multi-layered pyramidal-to-pyramidal circuits at the inception of neocortex, and studying these circuits could yield insights into the etiology of autism.
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6. Ochoa-Lubinoff C, Makol BA, Dillon EF. Autism in Women. Neurologic clinics. 2023; 41(2): 381-97.
Relative to males, women with autism spectrum disorder (ASD) have neurobiological and clinical presentation differences. Recent research suggests that the male/female ASD prevalence gap is smaller than previously reported. Sex differences in symptom presentation as well as the male bias of ASD account for delayed/missed diagnosis among women. Investigating ASD and providing psychological evaluation referrals for women who are struggling socially and present with complex mental health conditions (e.g., ADHD, depression), even when they do not show typical autistic characteristics, is important. Accurate diagnosis facilitates understanding of challenges, increases access to treatments, and alleviates the burden of ASD.
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7. Quetsch LB, Brown C, Onovbiona H, Bradley R, Aloia L, Kanne S. Understanding aggression in autism across childhood: Comparisons with a non-autistic sample. Autism research : official journal of the International Society for Autism Research. 2023.
As many as half of all autistic youth face challenges with aggression. And while research in this area is growing, the prevalence and characterization of aggressive behaviors across autistic development remains poorly understood. This lack of knowledge on the autistic experience is further clouded as aggression is rarely compared against non-autistic youth samples. To address this gap in the literature, the present study compared autistic children (N = 450) to non-autistic children (N = 432) on multiple caregiver-report measures of aggressive behavior and associated constructs (i.e., anger, disruptive behavior) across key developmental periods (<6, 6-12, 13-17 years) via a cross-sectional design. Outcomes indicated higher levels of verbal aggression and behavioral intensity for autistic youth across development. Further, autistic children under age 6 had more significant levels of physical aggression than non-autistic peers; however, these levels became equal to non-autistic peers as the youths aged. Implications for differences in the presence of aggressive behavior as well as possible treatment options for aggression are discussed.
