Optogenetic Targeting of Astrocytes Restores Slow Brain Rhythm Function and Slows Alzheimer’s Disease Pathology

• DOI: 10.21203/rs.3.rs-2813056/v1
• Publication Date: 2023-04-25T18:22:43Z
• Authors: Yee Fun Lee; Alyssa N. Russ; Qiuchen Zhao; Megi Maci; Morgan R. Miller; Steven S. Hou; Moustafa Algamal; Zhuoyang Zhao; Hanyan Li; Noah Gelwan; Stephen N. Gomperts; Alfonso Araque; Elena Galea; Brian J. Bacskai; Ksenia V. Kastanenka

Abstract Patients with Alzheimer’s disease (AD) exhibit non-rapid eye movement (NREM) sleep disturbances in addition to memory deficits. Disruption of NREM slow waves occurs early the progression and is recapitulated transgenic mouse models beta-amyloidosis. However, mechanisms underlying slow-wave disruptions remain unknown. Because astrocytes contribute activity, we used multiphoton microscopy optogenetics investigate whether they APP mice. The power but not frequency astrocytic calcium transients was reduced mice compared nontransgenic controls. Optogenetic activation at endogenous restored power, amyloid deposition, prevented neuronal elevations, improved performance. Our findings revealed malfunction network driving disruptions. Thus, targeting restore circuit activity AD could ameliorate progression.