1. Bemben MA, Nguyen QA, Wang T, Li Y, Nicoll RA, Roche KW. {{Autism-associated mutation inhibits protein kinase C-mediated neuroligin-4X enhancement of excitatory synapses}}. {Proc Natl Acad Sci U S A};2015 (Feb 9)
Autism spectrum disorders (ASDs) comprise a highly heritable, multifarious group of neurodevelopmental disorders, which are characterized by repetitive behaviors and impairments in social interactions. Point mutations have been identified in X-linked Neuroligin (NLGN) 3 and 4X genes in patients with ASDs and all of these reside in their extracellular domains except for a single point mutation in the cytoplasmic domain of NLGN4X in which an arginine is mutated to a cysteine (R704C). Here we show that endogenous NLGN4X is robustly phosphorylated by protein kinase C (PKC) at T707, and R704C completely eliminates T707 phosphorylation. Endogenous NLGN4X is intensely phosphorylated on T707 upon PKC stimulation in human neurons. Furthermore, a phospho-mimetic mutation at T707 has a profound effect on NLGN4X-mediated excitatory potentiation. Our results now establish an important interplay between a genetic mutation, a key posttranslational modification, and robust synaptic changes, which can provide insights into the synaptic dysfunction of ASDs.
Lien vers le texte intégral (Open Access ou abonnement)
2. Purkayastha P, Malapati A, Yogeeswari P, Sriram D. {{A Review on GABA/Glutamate Pathway for Therapeutic Intervention of ASD and ADHD}}. {Curr Med Chem};2015 (Feb 9)
Balance between excitatory glutamate and inhibitory GABA neurotransmitter is essential and critical for proper development and functioning of brain. GABAergic (gamma aminobutyric acid) and glutamatergic interneurons maintain excitability, integrity and synaptic plasticity. Several evidences implicated relative loss of inhibitory GABA with corresponding glutamate mediated hyper-excitation in development of autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). ASD is the common neurological disorder with an estimated relative occurrence of 0.5-1% of universal population. Several studies demonstrated the imbalance of excitatory/inhibitory neurotransmitters resulting from neurodevelopmental impairments in glutamatergic and GABAergic system, which might resemblesa common pathological mechanism for the developmental disorders. This review focuses on the necessity for developing GABA enhancing and glutamate suppressing drug candidates and illustrates the role of GABAergic and glutamatergic system in cognition and memory impairment involved in neurodevelopmental disorders with emphasis on ASD and ADHD. The review also highlights the newly emerging drugs for neurodevelopmental disorders.
3. Stewart ME, Allison C, Baron-Cohen S, Watson R. {{Investigating the Structure of the Autism-Spectrum Quotient Using Mokken Scaling}}. {Psychol Assess};2015 (Feb 9)
Traits similar to those shown in autism spectrum condition (ASC) are apparent in relatives of individuals with ASC, and in the general population without necessarily meeting diagnostic criteria for an ASC. We assess whether the Autism-Spectrum Quotient (AQ), a self-report measure, has hierarchical properties using Mokken scaling. Hierarchical scales allow the presence of a latent trait to be identified by discovering whether and how many specific items form an ordered array along it. Data were collected from 2 groups: (1) people with ASC (n = 449: 240 males, 209 females, Mage 35.4 years, SD = 12.8) and (2) university students (n = 943: 465 males, 475 females, Mage = 23.0 years, SD = 8.4). A single Mokken scale was obtained in the data from university students and 3 scales were obtained in the data from people with ASC. The scales all showed moderate Mokken scaling properties with the single scale obtained from university students showing weak invariant item ordering and 2 of the scales from people with ASC showing weak invariant item ordering. The AQ formed reliable Mokken scales. There was a large overlap between the scale from the university student sample and the sample with ASC, with the first scale, relating to social interaction, being almost identical. The present study confirms the utility of the AQ as a single instrument that can dimensionalize autistic traits in both university student and clinical samples of ASC, and confirms that items of the AQ are consistently ordered relative to one another. (PsycINFO Database Record (c) 2015 APA, all rights reserved).
