| Autor: |
Lee YF; Boston University School of Medicine., Russ AN; Massachusetts General Hospital, Harvard Medical School., Zhao Q; Massachusetts General Hospital, Harvard Medical School., Maci M; Massachusetts General Hospital, Harvard Medical School., Miller MR; Massachusetts General Hospital, Harvard Medical School., Hou SS; Massachusetts General Hospital, Harvard Medical School., Algamal M; Massachusetts General Hospital, Harvard Medical School., Zhao Z; Massachusetts General Hospital, Harvard Medical School., Li H; Massachusetts General Hospital, Harvard Medical School., Gelwan N; Massachusetts General Hospital, Harvard Medical School., Gomperts SN; Massachusetts General Hospital, Harvard Medical School., Araque A; University of Minnesota., Galea E; Massachusetts General Hospital, Harvard Medical School., Bacskai BJ; Massachusetts General Hospital, Harvard Medical School., Kastanenka KV; Massachusetts General Hospital, Harvard Medical School. |
| Abstrakt: |
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 in the disease progression and is recapitulated in transgenic mouse models of beta-amyloidosis. However, the mechanisms underlying slow-wave disruptions remain unknown. Because astrocytes contribute to slow-wave activity, we used multiphoton microscopy and optogenetics to investigate whether they contribute to slow-wave disruptions in APP mice. The power but not the frequency of astrocytic calcium transients was reduced in APP mice compared to nontransgenic controls. Optogenetic activation of astrocytes at the endogenous frequency of slow waves restored slow-wave power, reduced amyloid deposition, prevented neuronal calcium elevations, and improved memory performance. Our findings revealed malfunction of the astrocytic network driving slow-wave disruptions. Thus, targeting astrocytes to restore circuit activity underlying sleep and memory disruptions in AD could ameliorate disease progression. |
