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- Title
Restoring activity in the thalamic reticular nucleus improves sleep architecture and reduces Aβ accumulation in mice.
- Authors
Jagirdar, Rohan; Fu, Chia-Hsuan; Park, Jin; Corbett, Brian F.; Seibt, Frederik M.; Beierlein, Michael; Chin, Jeannie
- Abstract
Exciting the thalamus for more sleep and less amyloid: Recent data demonstrated a link between sleep disturbances and Alzheimer's disease (AD). However, our understanding of the mechanisms mediating sleep disturbances in AD remains incomplete. Here, Jagirdar et al. show that the thalamic reticular nucleus (TRN) plays a main role in determining the effects of sleep on hallmarks of AD in mice and possibly in patients. TRN activity was reduced in a mouse model of AD, resulting in reduced slow-wave sleep (SWS), and its activation restored SWS and reduced amyloid plaques in multiple brain areas. In patients with AD, markers of TRN activation correlated with disease stage. Targeting TRN activation might have therapeutic effects in AD. Sleep disruptions promote increases of amyloid β (Aβ) and tau in the brain and increase Alzheimer's disease (AD) risk, but the precise mechanisms that give rise to sleep disturbances have yet to be defined. The thalamic reticular nucleus (TRN) is essential for sleep maintenance and for the regulation of slow-wave sleep (SWS). We examined the TRN in transgenic mice that express mutant human amyloid precursor protein (APP) and found reduced neuronal activity, increased sleep fragmentation, and decreased SWS time as compared to nontransgenic littermates. Selective activation of the TRN using excitatory DREADDs restored sleep maintenance, increased time in SWS, and reduced amyloid plaque load in both hippocampus and cortex. Our findings suggest that the TRN may play a major role in symptoms associated with AD. Enhancing TRN activity might be a promising therapeutic strategy for AD.
- Subjects
THALAMIC nuclei; NON-REM sleep; TRANSGENIC mice; AMYLOID beta-protein precursor; LABORATORY mice; SLOW wave sleep; SLEEP
- Publication
Science Translational Medicine, 2021, Vol 13, Issue 618, p1
- ISSN
1946-6234
- Publication type
Article
- DOI
10.1126/scitranslmed.abh4284