Mutant β 1 -adrenergic receptor improves REM sleep and ameliorates tau accumulation in a mouse model of tauopathy

• Published in: Proceedings of the National Academy of Sciences - PNAS 2023-04, Vol.120 (15), p.e2221686120
• Main Authors: Dong, Qing, Ptáček, Louis J, Fu, Ying-Hui
• Format: Article
• Language: English
• Subjects: Animals; Disease Models, Animal; Locus Coeruleus - metabolism; Mice; Mice, Transgenic; Receptors, Adrenergic; Sleep - physiology; Sleep Wake Disorders; Sleep, REM; tau Proteins - genetics; tau Proteins - metabolism; Tauopathies - genetics
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2221686120

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 in mice, 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 the background. We found that the mutation helped restore rapid eye movement (REM) sleep and alleviated tau aggregation in a sleep-wake center, the locus coeruleus (LC), in mice. We found that ADRB1 neurons in the central amygdala (CeA) sent projections to the LC, and stimulating CeA neuron activity increased REM sleep. Furthermore, the mutant attenuated tau spreading from the CeA to the LC. Our findings suggest that the mutation protects against tauopathy by both mitigating tau accumulation and attenuating tau spreading.