Validating γ oscillations and delayed auditory responses as translational biomarkers of autism.
Validating γ oscillations and delayed auditory responses as translational biomarkers of autism.
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DOI：
10.1016/j.biopsych.2010.09.031
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发表时间：
2010-12-15
影响因子：
10.6
通讯作者：
Siegel, Steven J.
中科院分区：
文献类型：
--
作者：
Gandal, Michael J.;Edgar, J. Christopher;Ehrlichman, Richard S.;Mehta, Mili;Roberts, Timothy P. L.;Siegel, Steven J.
啮齿动物复杂行为表型（例如语言）建模的困难阻碍了自闭症谱系障碍（ASD）的病理生理学研究和治疗开发。然而，最近的人类神经影像学研究已经确定了与自闭症谱系障碍的异常神经动力学更直接相关的功能性生物标志物。这项研究在小鼠和人类自闭症平行研究中评估了自闭症听觉诱发反应内表型的转化潜力。在纯音听觉呈现过程中，对 17 名正常发育儿童和 25 名自闭症儿童进行了全皮层脑磁图记录。在时域和频域中分析颞上回活动。记录产前暴露于丙戊酸（VPA）的小鼠的听觉诱发电位，并用类似方法进行分析。暴露于 VPA 的小鼠表现出与自闭症相关的选择性行为改变，包括社交互动和超声波发声减少、重复性自我梳理增加以及前脉冲抑制缺陷。自闭症受试者和暴露于 VPA 的小鼠在 N1/M100 诱发反应中表现出类似的 10% 潜伏期延迟，并且伽马频率 (30–50 Hz) 锁相因子 (PLF) 降低。电生理学测量与小鼠行为缺陷相关。在小鼠中，γ PLF 与自闭症风险基因 Neuroligin-3 的表达相关，并且神经缺陷由 mGluR5 受体拮抗剂 MPEP 调节。结果证明了一种新的临床前方法来理解自闭症的机制和开发治疗方法。
Difficulty modeling complex behavioral phenotypes in rodents (e.g., language) has hindered pathophysiological investigation and treatment development for autism spectrum disorders (ASD). Recent human neuroimaging studies, however, have identified functional biomarkers that can be more directly related to the abnormal neural dynamics of ASD. This study assessed the translational potential of auditory evoked-response endophenotypes of autism in parallel mouse and human studies of autism. Whole-cortex magnetoencephalography was recorded in 17 typically developing and 25 autistic children during auditory pure-tone presentation. Superior temporal gyrus activity was analyzed in time and frequency domains. Auditory evoked potentials were recorded in mice prenatally exposed to valproic acid (VPA) and analyzed with analogous methods. VPA-exposed mice demonstrated selective behavioral alterations related to autism, including reduced social interactions and ultrasonic vocalizations, increased repetitive self-grooming, and prepulse inhibition deficits. Autistic subjects and VPA-exposed mice showed a similar 10% latency delay in the N1/M100 evoked response and a reduction in gamma frequency (30–50 Hz) phase-locking factor (PLF). Electrophysiological measures were associated with mouse behavioral deficits. In mice, gamma PLF was correlated with expression of the autism risk gene neuroligin-3 and neural deficits were modulated by the mGluR5-receptor antagonist MPEP. Results demonstrate a novel preclinical approach toward mechanistic understanding and treatment development for autism.
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影响因子：
4.9
作者：
Gogolla, Nadine;LeBlanc, Jocelyn J.;Quast, Kathleen B.;Sudhof, Thomas C.;Fagiolini, Michela;Hensch, Takao K.
通讯作者：
Hensch, Takao K.
影响因子：
4.4
作者：
Connolly, PM;Maxwell, C;Siegel, SJ
通讯作者：
Siegel, SJ
影响因子：
3.3
作者：
Gandal, M. J.;Ehrlichman, R. S.;Siegel, S. J.
通讯作者：
Siegel, S. J.
影响因子：
5.6
作者：
Eyal, S;Yagen, B;Bialer, M
通讯作者：
Bialer, M
DOI：
10.1124/jpet.109.150938
发表时间：
2009-10-01
影响因子：
3.5
作者：
Bodarky, Christina L.;Halene, Tobias B.;Siegel, Steven J.
通讯作者：
Siegel, Steven J.