Gamma Entrainment Binds Higher-Order Brain Regions and Offers Neuroprotection
Gamma Entrainment Binds Higher-Order Brain Regions and Offers Neuroprotection
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DOI：
10.1016/j.neuron.2019.04.011
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发表时间：
2019-06-05
期刊：
影响因子：
16.2
通讯作者：
Tsai, Li-Huei
中科院分区：
文献类型：
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作者：
Adaikkan, Chinnakkaruppan;Middleton, Steven J.;Tsai, Li-Huei
神经元和突触丢失是许多神经退行性疾病的特征，如额颞痴呆和阿尔茨海默病。最近，我们发现，在多种小鼠模型中，用视觉刺激(使用感觉刺激或属的伽马夹带)诱导伽马振荡可以减少淀粉样斑块和磷酸化的tau。属是否会影响神经退行性变或认知能力，目前尚不清楚。在这里，我们证明了在Tau P301S和CK-P25小鼠的神经变性模型中，Genus可以在视觉皮质、海马体和前额叶皮质引入伽玛振荡。在神经变性的早期阶段，Tau P301S和CK-p25小鼠受到慢性每日属神经变性的影响，表现出跨多个脑区的神经元和突触密度的保存和认知能力的改善。我们的转录和磷蛋白质组数据表明，慢性属改变神经元到较不退化的状态，改善突触功能，增强神经保护因子，减少神经元的DNA损伤，同时也减少小胶质细胞的炎症反应。
Neuronal and synaptic loss is characteristic in many neurodegenerative diseases, such as frontotemporal dementia and Alzheimer's disease. Recently, we showed that inducing gamma oscillations with visual stimulation (gamma entrainment using sensory stimuli, or GENUS) reduced amyloid plaques and phosphorylated tau in multiple mouse models. Whether GENUS can affect neurodegeneration or cognitive performance remains unknown. Here, we demonstrate that GENUS can entrain gamma oscillations in the visual cortex, hippocampus, and prefrontal cortex in Tau P301S and CK-p25 mouse models of neurodegeneration. Tau P301S and CK-p25 mice subjected to chronic, daily GENUS from the early stages of neurodegeneration showed a preservation of neuronal and synaptic density across multiple brain areas and modified cognitive performance. Our transcriptomic and phosphoproteomic data suggest that chronic GENUS shifts neurons to a less degenerative state, improving synaptic function, enhancing neuroprotective factors, and reducing DNA damage in neurons while also reducing inflammatory response in microglia.