Multi-sensory Gamma Stimulation Ameliorates Alzheimer's-Associated Pathology and Improves Cognition.,Cell

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Multi-sensory Gamma Stimulation Ameliorates Alzheimer's-Associated Pathology and Improves Cognition.
Cell ( IF 45.5 ) Pub Date : 2019-03-14 , DOI: 10.1016/j.cell.2019.02.014
Anthony J Martorell ₁ , Abigail L Paulson ₂ , Ho-Jun Suk ₃ , Fatema Abdurrob ₁ , Gabrielle T Drummond ₁ , Webster Guan ₄ , Jennie Z Young ₁ , David Nam-Woo Kim ₁ , Oleg Kritskiy ₁ , Scarlett J Barker ₁ , Vamsi Mangena ₅ , Stephanie M Prince ₂ , Emery N Brown ₆ , Kwanghun Chung ₇ , Edward S Boyden ₈ , Annabelle C Singer ₂ , Li-Huei Tsai ₉

Affiliation

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.
Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA 30332, USA.
McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; MIT Media Lab, Departments of Biological Engineering and Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Harvard-MIT Health Sciences and Technology, Cambridge, MA 02139, USA.
Department of Chemical Engineering, MIT, Cambridge, MA, USA.
Harvard-MIT Health Sciences and Technology, Cambridge, MA 02139, USA.
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; Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA; Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA; Harvard Medical School, Boston, MA 02115, USA.
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; Department of Chemical Engineering, MIT, Cambridge, MA, USA; Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02139, USA.
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; MIT Media Lab, Departments of Biological Engineering and Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
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; Broad Institute of Harvard and MIT, Cambridge, MA 02139, USA.

We previously reported that inducing gamma oscillations with a non-invasive light flicker (gamma entrainment using sensory stimulus or GENUS) impacted pathology in the visual cortex of Alzheimer's disease mouse models. Here, we designed auditory tone stimulation that drove gamma frequency neural activity in auditory cortex (AC) and hippocampal CA1. Seven days of auditory GENUS improved spatial and recognition memory and reduced amyloid in AC and hippocampus of 5XFAD mice. Changes in activation responses were evident in microglia, astrocytes, and vasculature. Auditory GENUS also reduced phosphorylated tau in the P301S tauopathy model. Furthermore, combined auditory and visual GENUS, but not either alone, produced microglial-clustering responses, and decreased amyloid in medial prefrontal cortex. Whole brain analysis using SHIELD revealed widespread reduction of amyloid plaques throughout neocortex after multi-sensory GENUS. Thus, GENUS can be achieved through multiple sensory modalities with wide-ranging effects across multiple brain areas to improve cognitive function.

中文翻译：

多感官伽马刺激改善阿尔茨海默氏症相关病理并改善认知。

我们以前曾报道过，用非侵入性闪烁（伽马夹带使用感官刺激或GENUS）诱导伽马振荡会影响阿尔茨海默氏病小鼠模型的视觉皮层中的病理。在这里，我们设计了听觉音调刺激，以驱动听觉皮层（AC）和海马CA1中的伽马频率神经活动。7天的听觉GENUS改善了5XFAD小鼠的AC和海马中的空间和识别记忆，并减少了淀粉样蛋白。激活反应的变化在小胶质细胞，星形胶质细胞和脉管系统中很明显。听觉GENUS还可以减少P301S tauopathy模型中的磷酸化tau蛋白。此外，听觉和视觉的GENUS结合在一起产生了小胶质细胞簇反应，但内侧前额叶皮层的淀粉样蛋白却减少了，但不是单独一个。使用SHIELD进行的全脑分析显示，多感官GENUS后，整个新皮层的淀粉样斑块减少了。因此，可以通过多种感觉方式来实现GENUS，这种感觉方式可以跨越多个大脑区域来产生广泛的作用，从而改善认知功能。

更新日期：2019-03-15

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