The deubiquitinase USP6 affects memory and synaptic plasticity through modulating NMDA receptor stability

by Fanwei Zeng, Xuehai Ma, Lin Zhu, Qiang Xu, Yuzhe Zeng, Yue Gao, Guilin Li, Tiantian Guo, Haibin Zhang, Xiaoyan Tang, Ziqiang Wang, Zesen Ye, Liangkai Zheng, Hongfeng Zhang, Qiuyang Zheng, Kunping Li, Jinfang Lu, Xueting Qi, Hong Luo, Xian Zhang, Zhanxiang Wang, Yulin Zhou, Yi Yao, Rongqin Ke, Ying Zhou, Yan Liu, Hao Sun, Timothy Huang, Zhicheng Shao, Huaxi Xu, Xin Wang Ubiquitin-specific protease (USP) 6 is a hominoid deubiquitinating enzyme previously implicated in intellectual disability and autism spectrum disorder. Although these findings link USP6 to higher brain function, potential roles for USP6 in cognition have not been investigated. Here, we report tha t USP6 is highly expressed in induced human neurons and that neuron-specific expression of USP6 enhances learning and memory in a transgenic mouse model. Similarly, USP6 expression regulatesN-methyl-D-aspartate-type glutamate receptor (NMDAR)-dependent long-term potentiation and long-term depression in USP6 transgenic mouse hippocampi. Proteomic characterization of transgenic USP6 mouse cortex reveals attenuated NMDAR ubiquitination, with concomitant elevation in NMDAR expression, stability, and cell surface distribution with USP6 overexpression. USP6 positively modulates GluN1 expression in transfected cells, and USP6 down-regulation impedes focal GluN1 distribution at postsynaptic densities and impairs synaptic function in neurons derived from human embryonic stem cells. Together, these results indicate that USP...
Source: PLoS Biology: Archived Table of Contents - Category: Biology Authors: Source Type: research

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ConclusionsThese preliminary data suggest that while individuals might frame their self-injury as a positive or neutral thing, there remains a concerning relationship between self-injury and suicidality which exists regardless of individual feelings on self-injury. This is consistent with the theoretical perspective that self-injury can be a “gateway” through which individuals acquire capability for lethal suicidal behaviors. The data highlight that particular methods (cutting) and reasons for self-injury may be of significant concern, but this information, which might be of extreme value for clinicians, requir...
Source: Molecular Autism - Category: Molecular Biology Source Type: research
Parents caring for their adult children with communication disorders walk a tight rope. They precariously inch along the wire of life, balancing their own responsibilities plus those of their children. They also balance myriad schedules, health care professionals, therapies, medications, and special equipment necessary for activities of daily living. Many of these visionary parents rejected the prevailing past trends to institutionalize their children. These parents might have been active in making sure their children received appropriate services in school, or home schooled. Many also advocated to change laws improving e...
Source: American Speech-Language-Hearing Association (ASHA) Press Releases - Category: Speech-Language Pathology Authors: Tags: Academia & Research Health Care Private Practice Slider Speech-Language Pathology Autism Spectrum Disorder Source Type: blogs
ConclusionsOur results indicate the prevalence of multiple comorbidities varies across the lifespan in DS, and in adults, rates for psychiatric comorbidities show different patterns for males and females relative to expected population rates. Further, most health comorbidities are not associated with poorer cognitive outcomes in DS, apart from autism and epilepsy. It is essential for clinicians to consider such differences to provide appropriate care and treatment for those with DS and to provide prognostic information relating to cognitive outcomes in those with comorbidities.
Source: Journal of Neurodevelopmental Disorders - Category: Neurology Source Type: research
___ Parents pay thousands for ‘brain training’ to help kids with ADHD and autism. But does it work? (NBC News): “…As the number of children diagnosed with ADHD and autism surges in the U.S., according to federal data, and as parents become exasperated with treatments that don’t work or involve medications that carry the risk of side effects, neurotechnology industry analysts predict the demand for programs like these will only grow… Much of the growth in brain training is in apps and games that people use at home or in school, said Alvaro Fernandez, CEO of SharpBrains, a research firm ...
Source: SharpBrains - Category: Neuroscience Authors: Tags: Cognitive Neuroscience Education & Lifelong Learning Technology adhd autism Brain Balance brain training brain training centers BrainRx Direct-to-Consumer LearningRx Neurotechnology Source Type: blogs
ConclusionsAutistic mothers face unique challenges and the stigma associated with autism may further exacerbate communication difficulties. Greater understanding and acceptance amongst individuals who interact with autistic mothers is needed, and autistic mothers would benefit from additional and better-tailored support.
Source: Molecular Autism - Category: Molecular Biology Source Type: research
ConclusionsThe proposed CSHQ five-factor model may be useful in future studies of sleep problems in young children with ASD.
Source: Research in Developmental Disabilities - Category: Disability Source Type: research
Abstract Irritability and aggression (IA) are highly prevalent in individuals with autism spectrum disorder (ASD). Although clinical correlates of IA in this population have been previously examined, findings from existing studies capturing symptoms as a set of latent variables do not fully explain meaningful associations between the symptoms themselves. In the present study, we conducted network analysis which conceptualizes mental health difficulties as a complex network of directly associated symptoms in 2612 individuals who were diagnosed with ASD through rigorous diagnostic assessment and who were enrolled in...
Source: Journal of Autism and Developmental Disorders - Category: Psychiatry Authors: Tags: J Autism Dev Disord Source Type: research
Conclusion: the systematic review could help health specialists and other professionals to identify evidence-based strategies to deal with child and adolescents with mental health conditions.
Source: Medicine - Category: Internal Medicine Tags: Research Article: Study Protocol Systematic Review Source Type: research
In this report, we describe the prevalence and disease burden of each mental disorder for the states of India, from 1990 to 2017.MethodsWe used all accessible data from multiple sources to estimate the prevalence of mental disorders, years lived with disability (YLDs), and disability-adjusted life-years (DALYs) caused by these disorders for all the states of India from 1990 to 2017, as part of the Global Burden of Diseases, Injuries, and Risk Factors Study. We assessed the heterogeneity and time trends of mental disorders across the states of India. We grouped states on the basis of their Socio-demographic Index (SDI), whi...
Source: The Lancet Psychiatry - Category: Psychiatry Source Type: research
Suicidality is significantly more common in autistic adults than the general population, yet the factors that increase risk for suicidality among autistic adults remain largely unknown. We identified characteristics associated with suicidal ideation and su...
Source: SafetyLit - Category: International Medicine & Public Health Tags: Age: Elder Adults Source Type: news
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