Fragile X Syndrome (FXS) is a leading known genetic cause of intellectual disability. Many symptoms of FXS overlap with those in autism including repetitive behaviors, language delays, anxiety, social impairments and sensory processing deficits. Electroencephalogram (EEG) recordings from humans with FXS and an animal model, the Fmr1 knockout (KO) mouse, show remarkably similar phenotypes suggesting that EEG phenotypes can serve as biomarkers for developing treatments. This includes enhanced resting gamma band power and sound evoked total power, and reduced fidelity of temporal processing and habituation of responses to repeated sounds. Given the therapeutic potential of the antibiotic minocycline in humans with FXS and animal models, it is important to determine sensitivity and selectivity of EEG responses to minocycline. Therefore, in this study, we examined if a 10-day treatment of adult Fmr1 KO mice with minocycline (oral gavage, 30 mg/kg per day) would reduce EEG abnormalities. We tested if minocycline treatment has specific effects based on the EEG measurement type (e.g., resting versus sound-evoked) from the frontal and auditory cortex of the Fmr1 KO mice. We show increased resting EEG gamma power and reduced phase locking to time varying stimuli as well as the 40 Hz auditory steady state response in the Fmr1 KO mice in the pre-drug condition. Minocycline treatment increased gamma band phase locking in response to auditory stimuli, and reduced sound-evoked power of auditory event related potentials (ERP) in Fmr1 KO mice compared to vehicle treatment. Minocycline reduced resting EEG gamma power in Fmr1 KO mice, but this effect was similar to vehicle treatment. We also report frequency band-specific effects on EEG responses. Taken together, these data indicate that sound-evoked EEG responses may serve as more sensitive measures, compared to resting EEG measures, to isolate minocycline effects from placebo in humans with FXS. Given the use of minocycline and EEG recordings in a number of neurodegenerative and neurodevelopmental conditions, these findings may be more broadly applicable in translational neuroscience.

中文翻译：

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米诺环素治疗可逆转脆性 X 综合征小鼠模型中声音诱发的脑电图异常

脆性 X 综合征 (FXS) 是导致智力障碍的主要已知遗传原因。FXS 的许多症状与自闭症的症状重叠，包括重复行为、语言延迟、焦虑、社交障碍和感觉处理缺陷。来自患有 FXS 的人类和动物模型 Fmr1 敲除 (KO) 小鼠的脑电图 (EEG) 记录显示出非常相似的表型，表明 EEG 表型可以作为开发治疗的生物标志物。这包括增强的静息伽马波段功率和声音诱发的总功率，以及降低时间处理的保真度和对重复声音的反应习惯。鉴于抗生素米诺环素在人类 FXS 和动物模型中的治疗潜力，确定 EEG 对米诺环素反应的敏感性和选择性非常重要。因此，在本研究中，我们检查了用米诺环素（口服强饲法，每天 30 毫克/千克）对成年 Fmr1 KO 小鼠进行 10 天治疗是否会减少 EEG 异常。我们测试了米诺环素治疗是否具有基于 Fmr1 KO 小鼠额叶和听觉皮层的 EEG 测量类型（例如，静息与声音诱发）的特定影响。我们显示，在药物前条件下，Fmr1 KO 小鼠的静息 EEG 伽马功率增加，对时变刺激的锁相减少，以及 40 Hz 听觉稳态响应。与载体治疗相比，米诺环素治疗增加了响应听觉刺激的伽马带锁相，并降低了 Fmr1 KO 小鼠听觉事件相关电位 (ERP) 的声音诱发能力。米诺环素降低了 Fmr1 KO 小鼠的静息 EEG 伽玛功率，但这种效果与载体治疗相似。我们还报告了特定频段对 EEG 反应的影响。总之，这些数据表明，与静息 EEG 测量相比，声音诱发的 EEG 反应可以作为更敏感的测量，以将米诺环素与安慰剂对 FXS 患者的影响隔离开来。鉴于在许多神经退行性疾病和神经发育疾病中使用米诺环素和脑电图记录，这些发现可能更广泛地适用于转化神经科学。