Mutant β-adrenergic receptor improves REM sleep and ameliorates tau accumulation in a mouse model of tauopathy.

Abstract

Sleep is essential for our well-being, and chronic sleep deprivation has unfavorable health consequences. We recently demonstrated that two familial natural short sleep (FNSS) mutations,and, are strong genetic modifiers of tauopathy inmice, a model of tauopathy. To gain more insight into how FNSS variants modify the tau phenotype, we tested the effect of another FNSS gene variant,, by crossing mice with this mutation onto thebackground. We found that themutation helped restore rapid eye movement (REM) sleep and alleviated tau aggregation in a sleep-wake center, the locus coeruleus (LC), inmice. We found that ADRB1neurons in the central amygdala (CeA) sent projections to the LC, and stimulating CeAneuron activity increased REM sleep. Furthermore, the mutantattenuated tau spreading from the CeA to the LC. Our findings suggest that themutation protects against tauopathy by both mitigating tau accumulation and attenuating tau spreading.