Noninvasive 40-Hz light flicker to recruit microglia and reduce amyloid beta load
Noninvasive 40-Hz light flicker to recruit microglia and reduce amyloid beta load
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DOI：
10.1038/s41596-018-0021-x
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发表时间：
2018-08-01
期刊：
影响因子：
14.8
通讯作者：
Tsai, Li-Huei
中科院分区：
文献类型：
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作者：
Singer, Annabelle C.;Martorell, Anthony J.;Tsai, Li-Huei
小胶质细胞是大脑的主要免疫细胞，在大脑的病理和正常功能中起着关键作用。越来越多的努力旨在揭示这些细胞如何被利用来治疗阿尔茨海默氏症等神经退行性疾病以及精神分裂症和自闭症等发育障碍。我们最近发现，使用非侵入性暴露于40-赫兹白光(4,000 K)闪烁来驱动40-赫兹神经活动可以将小胶质细胞转变为吞噬状态，并减少淀粉样β蛋白，这是一种被认为在阿尔茨海默病(AD)中引发神经毒性事件的多肽。本文描述了如何构建基于LED的闪光装置，将动物暴露在40赫兹的闪光和控制条件下，并进行下游测试以研究这些刺激的影响。与使用光遗传学驱动40赫兹的活动相比，光闪烁简单、实现更快且非侵入性；然而，它不像光遗传学可以实现的那样针对特定的细胞类型。这种驱动40赫兹神经活动的非侵入性方法应该能够进一步研究神经活动、分子病理学和大脑免疫系统之间的相互作用。构建闪光系统需要类似于1天的时间，并需要一些电子经验或可用的指导。闪烁操作和评估可以在几天内完成，具体取决于实验设计。
Microglia, the primary immune cells of the brain, play a key role in pathological and normal brain function. Growing efforts aim to reveal how these cells may be harnessed to treat both neurodegenerative diseases such as Alzheimer's and developmental disorders such as schizophrenia and autism. We recently showed that using noninvasive exposure to 40-Hz white-light (4,000 K) flicker to drive 40-Hz neural activity transforms microglia into an engulfing state and reduces amyloid beta, a peptide thought to initiate neurotoxic events in Alzheimer's disease (AD). This article describes how to construct an LED-based light-flicker apparatus, expose animals to 40-Hz flicker and control conditions, and perform downstream assays to study the effects of these stimuli. Light flicker is simple, faster to implement, and noninvasive, as compared with driving 40-Hz activity using optogenetics; however, it does not target specific cell types, as is achievable with optogenetics. This noninvasive approach to driving 40-Hz neural activity should enable further research into the interactions between neural activity, molecular pathology, and the brain's immune system. Construction of the light-flicker system requires similar to 1 d and some electronics experience or available guidance. The flicker manipulation and assessment can be completed in a few days, depending on the experimental design.