Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Laboratory for Circuit and Behavioral Physiology, RIKEN Center for Brain Science, Wako-shi, Saitama 351-0198, Japan.
Neuron. 2019 Jun 5;102(5):929-943.e8. doi: 10.1016/j.neuron.2019.04.011. Epub 2019 May 7.
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.
神经元和突触的丧失是许多神经退行性疾病的特征，如额颞叶痴呆和阿尔茨海默病。最近，我们发现通过视觉刺激诱导伽马振荡（使用感觉刺激的伽马同步，或 GENUS）可以减少多种小鼠模型中的淀粉样斑块和磷酸化 tau。然而，GENUS 是否可以影响神经退行性变或认知表现尚不清楚。在这里，我们证明 GENUS 可以使 Tau P301S 和 CK-p25 神经退行性变小鼠模型的视觉皮层、海马体和前额叶皮层中的伽马振荡同步。从神经退行性变的早期开始，接受慢性、每日 GENUS 的 Tau P301S 和 CK-p25 小鼠在多个脑区表现出神经元和突触密度的保持以及认知表现的改善。我们的转录组学和磷酸化蛋白质组学数据表明，慢性 GENUS 将神经元转变为一种退行性较小的状态，改善突触功能，增强神经保护因子，减少神经元中的 DNA 损伤，同时减少小胶质细胞中的炎症反应。
