The Parvalbumin Hypothesis of Autism Spectrum Disorder.
The Parvalbumin Hypothesis of Autism Spectrum Disorder.
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DOI：
10.3389/fncel.2020.577525
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发表时间：
2020
影响因子：
5.3
通讯作者：
Schwaller B
中科院分区：
文献类型：
--
作者：
Filice F;Janickova L;Henzi T;Bilella A;Schwaller B
自闭症谱系障碍（ASD）——一种神经发育障碍——的患病率正在上升，在北美、亚洲和欧洲约为2%。除了已知的遗传联系外，环境、表观遗传和代谢因素也与ASD的病因有关。虽然在行为层面上是高度异质性的，但ASD包括一系列核心症状，包括沟通和社会互动技能受损，以及刻板和重复的行为。这导致了一种说法，即大部分的ASD表型是由少数常见的信号通路的变化引起的，识别这些信号通路是自闭症研究的一个基本目标。利用先进的生物信息学工具和丰富的遗传数据，可以根据细胞功能和途径对大量asd相关基因进行分类。已知在ASD中受损的细胞过程包括基因调控、影响兴奋/抑制平衡的突触传递、神经元Ca2+信号、短/远程连接（电路和网络）的发展以及线粒体功能。这种改变通常发生在出生后早期的神经发育过程中。在ASD和精神分裂症中受影响最大的神经元是那些表达Ca2+结合蛋白小白蛋白（PV）的神经元。这些主要是抑制性中间神经元存在于人类和啮齿动物的许多不同的大脑区域，其特点是快速，非适应性放电，并且具有高能量需求。在人类ASD脑样本和小鼠ASD（和精神分裂症）模型中，PV在信使RNA （mRNA）和蛋白质水平上的表达经常降低。虽然人类PVALB基因不是这两种疾病的高易感性/风险基因，目前只在SFARI基因档案中列出，但我们提出并提供了支持Parvalbumin假说的证据，该假说认为PV水平降低与ASD（可能还有精神分裂症）的病因有关。
The prevalence of autism spectrum disorder (ASD)—a type of neurodevelopmental disorder—is increasing and is around 2% in North America, Asia, and Europe. Besides the known genetic link, environmental, epigenetic, and metabolic factors have been implicated in ASD etiology. Although highly heterogeneous at the behavioral level, ASD comprises a set of core symptoms including impaired communication and social interaction skills as well as stereotyped and repetitive behaviors. This has led to the suggestion that a large part of the ASD phenotype is caused by changes in a few and common set of signaling pathways, the identification of which is a fundamental aim of autism research. Using advanced bioinformatics tools and the abundantly available genetic data, it is possible to classify the large number of ASD-associated genes according to cellular function and pathways. Cellular processes known to be impaired in ASD include gene regulation, synaptic transmission affecting the excitation/inhibition balance, neuronal Ca2+ signaling, development of short-/long-range connectivity (circuits and networks), and mitochondrial function. Such alterations often occur during early postnatal neurodevelopment. Among the neurons most affected in ASD as well as in schizophrenia are those expressing the Ca2+-binding protein parvalbumin (PV). These mainly inhibitory interneurons present in many different brain regions in humans and rodents are characterized by rapid, non-adaptive firing and have a high energy requirement. PV expression is often reduced at both messenger RNA (mRNA) and protein levels in human ASD brain samples and mouse ASD (and schizophrenia) models. Although the human PVALB gene is not a high-ranking susceptibility/risk gene for either disorder and is currently only listed in the SFARI Gene Archive, we propose and present supporting evidence for the Parvalbumin Hypothesis, which posits that decreased PV level is causally related to the etiology of ASD (and possibly schizophrenia).
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DOI：
10.1017/s1461145712001216
发表时间：
2013-07
期刊：
The international journal of neuropsychopharmacology
影响因子：
--
作者：
Banerjee A;García-Oscos F;Roychowdhury S;Galindo LC;Hall S;Kilgard MP;Atzori M
通讯作者：
Atzori M
影响因子：
3.3
作者：
Chen, G.;Racay, P.;Schwaller, B.
通讯作者：
Schwaller, B.
影响因子：
25
作者：
Chen, Qian;Deister, Christopher A.;Feng, Guoping
通讯作者：
Feng, Guoping
影响因子：
3.7
作者：
Ariza, Jeanelle;Rogers, Haille;Martinez-Cerdeno, Veronica
通讯作者：
Martinez-Cerdeno, Veronica
影响因子：
15.9
作者：
Celio, MR;Spreafico, R;Vitellaro-Zuccarello, L
通讯作者：
Vitellaro-Zuccarello, L