美国麻省理工学院Li-Huei Tsai团队发现，多感官γ刺激促进淀粉样蛋白的胶淋巴清除。相关论文于2024年2月28日在线发表在《自然》杂志上。

研究人员展示了多感官伽马刺激能促进5XFAD阿尔茨海默病小鼠模型皮层中，脑脊液的流入和间质液的流出。脑脊液的流入与沿星形胶质细胞内膜和扩张的脑膜淋巴管的aquaporin-4极化增加有关。抑制胶淋巴清除可消除多感官40赫兹刺激对淀粉样蛋白的清除。

利用化学遗传学操作和基因编码的神经肽信号传感器，研究人员发现血管活性肠肽中间神经元通过调节动脉搏动促进胶淋巴清除。这些研究结果建立了一种新的机制，其能招募胶淋巴系统清除脑淀粉样蛋白。

研究人员表示，流体在大脑中的胶淋巴运动可清除代谢废物。无创40赫兹刺激可促进多个脑区的40赫兹神经活动，并减轻阿尔茨海默病小鼠模型的病理变化。

附：英文原文

Title: Multisensory gamma stimulation promotes glymphatic clearance of amyloid

Author: Murdock, Mitchell H., Yang, Cheng-Yi, Sun, Na, Pao, Ping-Chieh, Blanco-Duque, Cristina, Kahn, Martin C., Kim, TaeHyun, Lavoie, Nicolas S., Victor, Matheus B., Islam, Md Rezaul, Galiana, Fabiola, Leary, Noelle, Wang, Sidney, Bubnys, Adele, Ma, Emily, Akay, Leyla A., Sneve, Madison, Qian, Yong, Lai, Cuixin, McCarthy, Michelle M., Kopell, Nancy, Kellis, Manolis, Piatkevich, Kiryl D., Boyden, Edward S., Tsai, Li-Huei

Issue&Volume: 2024-02-28

Abstract: The glymphatic movement of fluid through the brain removes metabolic waste1,2,3,4. Noninvasive 40Hz stimulation promotes 40Hz neural activity in multiple brain regions and attenuates pathology in mouse models of Alzheimer’s disease5,6,7,8. Here we show that multisensory gamma stimulation promotes the influx of cerebrospinal fluid and the efflux of interstitial fluid in the cortex of the 5XFAD mouse model of Alzheimer’s disease. Influx of cerebrospinal fluid was associated with increased aquaporin-4 polarization along astrocytic endfeet and dilated meningeal lymphatic vessels. Inhibiting glymphatic clearance abolished the removal of amyloid by multisensory 40Hz stimulation. Using chemogenetic manipulation and a genetically encoded sensor for neuropeptide signalling, we found that vasoactive intestinal peptide interneurons facilitate glymphatic clearance by regulating arterial pulsatility. Our findings establish novel mechanisms that recruit the glymphatic system to remove brain amyloid.

DOI: 10.1038/s41586-024-07132-6

Source: https://www.nature.com/articles/s41586-024-07132-6