Multisensory gamma stimulation promotes glymphatic clearance of amyloid.
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
Nature · 2024 · PMID 38418876 · 인용 307
The glymphatic movement of fluid through the brain removes metabolic waste1-4. Noninvasive 40 Hz stimulation promotes 40 Hz neural activity in multiple brain regions and attenuates pathology in mouse models of Alzheimer's disease5-8. 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 40 Hz 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.