Common circuit defect of excitatory-inhibitory balance in mouse models of autism.
Common circuit defect of excitatory-inhibitory balance in mouse models of autism.
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DOI：
10.1007/s11689-009-9023-x
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发表时间：
2009-06
影响因子：
4.9
通讯作者：
Hensch, Takao K.
中科院分区：
文献类型：
--
作者：
Gogolla, Nadine;LeBlanc, Jocelyn J.;Quast, Kathleen B.;Sudhof, Thomas C.;Fagiolini, Michela;Hensch, Takao K.
自闭症谱系障碍（ASD）的复杂性的一个统一解释可能在于兴奋/抑制（E/I）回路平衡在发展的关键时期的破坏。我们检查了通常驱动经验依赖性回路细化的小清蛋白（PV）阳性抑制性神经元（Hensch Nat Rev Neurosci 6：877-888）是否在异质性ASD小鼠模型中被破坏。我们对先前发表的ASD小鼠模型中的PV表达进行了荟萃分析，并分析了另外两种模型，反映了胚胎化学损伤（产前丙戊酸盐，VPA）或在人类患者中发现的单基因突变（神经连接素-3，NL-3 R451 C）。在多种ASD小鼠模型中，新皮质中的PV细胞减少。与对照组形成鲜明对比的是，VPA和NL-3小鼠模型均显示顶叶和枕叶皮质（但不包括下方区域CA 1）中半球PV细胞的不对称减少。ASD小鼠模型可能共享PV电路中断，为电路发展和自闭症治疗的潜在预防提供了新的见解。本文的在线版本（doi：10.1007/s11689-009-9023-x）包含补充材料，可供授权用户使用。
One unifying explanation for the complexity of Autism Spectrum Disorders (ASD) may lie in the disruption of excitatory/inhibitory (E/I) circuit balance during critical periods of development. We examined whether Parvalbumin (PV)-positive inhibitory neurons, which normally drive experience-dependent circuit refinement (Hensch Nat Rev Neurosci 6:877–888,), are disrupted across heterogeneous ASD mouse models. We performed a meta-analysis of PV expression in previously published ASD mouse models and analyzed two additional models, reflecting an embryonic chemical insult (prenatal valproate, VPA) or single-gene mutation identified in human patients (Neuroligin-3, NL-3 R451C). PV-cells were reduced in the neocortex across multiple ASD mouse models. In striking contrast to controls, both VPA and NL-3 mouse models exhibited an asymmetric PV-cell reduction across hemispheres in parietal and occipital cortices (but not the underlying area CA1). ASD mouse models may share a PV-circuit disruption, providing new insight into circuit development and potential prevention by treatment of autism. The online version of this article (doi:10.1007/s11689-009-9023-x) contains supplementary material, which is available to authorized users.
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