| First Author | Dong Q | Year | 2023 |
| Journal | Proc Natl Acad Sci U S A | Volume | 120 |
| Issue | 15 | Pages | e2221686120 |
| PubMed ID | 37014857 | Mgi Jnum | J:336396 |
| Mgi Id | MGI:7466081 | Doi | 10.1073/pnas.2221686120 |
| Citation | Dong Q, et al. (2023) Mutant beta(1)-adrenergic receptor improves REM sleep and ameliorates tau accumulation in a mouse model of tauopathy. Proc Natl Acad Sci U S A 120(15):e2221686120 |
| abstractText | 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, DEC2-P384R and Npsr1-Y206H, are strong genetic modifiers of tauopathy in PS19 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, Adrb1-A187V, by crossing mice with this mutation onto the PS19 background. We found that the Adrb1-A187V mutation helped restore rapid eye movement (REM) sleep and alleviated tau aggregation in a sleep-wake center, the locus coeruleus (LC), in PS19 mice. We found that ADRB1(+) neurons in the central amygdala (CeA) sent projections to the LC, and stimulating CeA(ADRB1+) neuron activity increased REM sleep. Furthermore, the mutant Adrb1 attenuated tau spreading from the CeA to the LC. Our findings suggest that the Adrb1-A187V mutation protects against tauopathy by both mitigating tau accumulation and attenuating tau spreading. |
