1. Alessandra B, Paola V, Giorgio F, Alessandro G, Marina M, Paolo M, Elisabetta M, Annio P, Arianna V, Abruzzo PM. {{Na(+) , K(+) -ATPase activity in children with autism spectrum disorder: Searching for the reason(s) of its decrease in blood cells}}. {Autism Res}. 2018.
Na(+) , K(+) -ATPase (NKA) activity, which establishes the sodium and potassium gradient across the cell membrane and is instrumental in the propagation of the nerve impulses, is altered in a number of neurological and neuropsychiatric disorders, including autism spectrum disorders (ASD). In the present work, we examined a wide range of biochemical and cellular parameters in the attempt to understand the reason(s) for the severe decrease in NKA activity in erythrocytes of ASD children that we reported previously. NKA activity in leukocytes was found to be decreased independently from alteration in plasma membrane fluidity. The different subunits were evaluated for gene expression in leukocytes and for protein expression in erythrocytes: small differences in gene expression between ASD and typically developing children were not apparently paralleled by differences in protein expression. Moreover, no gross difference in erythrocyte plasma membrane oxidative modifications was detectable, although oxidative stress in blood samples from ASD children was confirmed by increased expression of NRF2 mRNA. Interestingly, gene expression of some NKA subunits correlated with clinical features. Excess inhibitory metals or ouabain-like activities, which might account for NKA activity decrease, were ruled out. Plasma membrane cholesterol, but not phosphatidylcholine and phosphatidlserine, was slighty decreased in erythrocytes from ASD children. Although no compelling results were obtained, our data suggest that alteration in the erytrocyte lipid moiety or subtle oxidative modifications in NKA structure are likely candidates for the observed decrease in NKA activity. These findings are discussed in the light of the relevance of NKA in ASD. Autism Research 2018. (c) 2018 The Authors. Autism Research published by International Society for Autism Research and Wiley Periodicals, Inc. LAY SUMMARY: The activity of the cell membrane enzyme NKA, which is instrumental in the propagation of the nerve impulses, is severely decreased in erythrocytes from ASD children and in other brain disorders, yet no explanation has been provided for this observation. We strived to find a biological/biochemical cause of such alteration, but most queries went unsolved because of the complexity of NKA regulation. As NKA activity is altered in many brain disorders, we stress the relevance of studies aimed at understanding its regulation in ASD.
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2. Balaan C, Corley MJ, Eulalio T, Leite-Ahyo K, Pang APS, Fang R, Khadka VS, Maunakea AK, Ward MA. {{Juvenile Shank3b deficient mice present with behavioral phenotype relevant to autism spectrum disorder}}. {Behav Brain Res}. 2018.
Autism spectrum disorder (ASD) is a pervasive, multifactorial neurodevelopmental disorder diagnosed according to deficits in three behavioral domains: communication, social interaction, and stereotyped/repetitive behaviors. Mutations in Shank genes account for ~1% of clinical ASD cases with Shank3 being the most common gene variant. In addition to maintaining synapses and facilitating dendritic maturation, Shank genes encode master scaffolding proteins that build core complexes in the postsynaptic densities of glutamatergic synapses. Male mice with a deletion of the PDZ domain of Shank3 (Shank3B KO) were previously shown to display ASD-like behavioral phenotypes with reported self-injurious repetitive grooming and aberrant social interactions. Our goal was to extend these previous findings and use a comprehensive battery of highly detailed ASD-relevant behavioral assays including an assessment of mouse ultrasonic communication carried out on key developmental days and male and female Shank3B KO mice. We demonstrate that ASD-related behaviors, atypical reciprocal social interaction and indiscriminate repetitive grooming, are apparent in juvenile stages of development of Shank3B KO mice. Our findings underscore the importance of utilizing Shank mutant models to understand the impact of this gene in ASD etiology, which may enable future studies focusing on etiological gene-environment interactions in ASD.
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3. Horvath S, McDermott E, Reilly K, Arunachalam S. {{Acquisition of Verb Meaning From Syntactic Distribution in Preschoolers With Autism Spectrum Disorder}}. {Language, speech, and hearing services in schools}. 2018; 49(3s): 668-80.
Purpose: Our goal was to investigate whether preschool children with autism spectrum disorder (ASD) can begin to learn new word meanings by attending to the linguistic contexts in which they occur, even in the absence of visual or social context. We focused on verbs because of their importance for subsequent language development. Method: Thirty-two children with ASD, ages 2;1-4;5 (years;months), participated in a verb-learning task. In a between-subjects design, they were randomly assigned to hear novel verbs in either transitive or intransitive syntactic frames while watching an unrelated silent animation or playing quietly with a toy. In an eye-tracking test, they viewed two video scenes, one depicting a causative event (e.g., boy spinning girl) and the other depicting synchronous events (e.g., boy and girl waving). They were prompted to find the referents of the novel verbs, and their eye gaze was measured. Results: Like typically developing children in prior work, children with ASD who had heard the verbs in transitive syntactic frames preferred to look to the causative scene as compared to children who had heard intransitive frames. Conclusions: This finding replicates and extends prior work on verb learning in children with ASD by demonstrating that they can attend to a novel verb’s syntactic distribution absent relevant visual or social context, and they can use this information to assign the novel verb an appropriate meaning. We discuss points for future research, including examining individual differences that may impact success and contrasting social and nonsocial word-learning tasks directly.
