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篇目详细内容 |
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【篇名】 |
Convergent synaptic and circuit substrates underlying autism genetic risks |
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【刊名】 |
Frontiers in Biology |
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【刊名缩写】 |
Front. Biol.
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【ISSN】 |
1674-7984 |
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【EISSN】 |
1674-7992 |
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【DOI】 |
10.1007/s11515-014-1298-y |
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【出版社】 |
Higher Education Press and Springer-Verlag Berlin
Heidelberg |
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【出版年】 |
2014 |
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【卷期】 |
9
卷2期 |
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【页码】 |
137-150
页,共
14
页 |
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【作者】 |
Aaron MCGEE;
Guohui LI;
Zhongming LU;
Shenfeng QIU;
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【关键词】 |
autism spectrum disorders; development; risk genes; synapse; circuits; behavior; neurodevelopmental disorders |
【摘要】 |
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There has been a surge of diagnosis of autism spectrum disorders (ASD) over the past decade. While large, high powered genome screening studies of children with ASD have identified numerous genetic risk factors, research efforts to understanding how each of these risk factors contributes to the development autism has met with limited success. Revealing the mechanisms by which these genetic risk factors affect brain development and predispose a child to autism requires mechanistic understanding of the neurobiological changes underlying this devastating group of developmental disorders at multifaceted molecular, cellular and system levels. It has been increasingly clear that the normal trajectory of neurodevelopment is compromised in autism, in multiple domains as much as aberrant neuronal production, growth, functional maturation, patterned connectivity, and balanced excitation and inhibition of brain networks. Many autism risk factors identified in humans have been now reconstituted in experimental mouse models to allow mechanistic interrogation of the biological role of the risk gene. Studies utilizing these mouse models have revealed that underlying the enormous heterogeneity of perturbed cellular events, mechanisms directing synaptic and circuit assembly may provide a unifying explanation for the pathophysiological changes and behavioral endophenotypes seen in autism, although synaptic perturbations are far from being the only alterations relevant for ASD. In this review, we discuss synaptic and circuit abnormalities obtained from several prevalent mouse models, particularly those reflecting syndromic forms of ASD that are caused by single gene perturbations. These compiled results reveal that ASD risk genes contribute to proper signaling of the developing gene networks that maintain synaptic and circuit homeostasis, which is fundamental to normal brain development. |
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