Mutant ß1-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, 2023 04 11.
Article
em En
| MEDLINE
| ID: mdl-37014857
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, 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 CeAADRB1+ 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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transtornos do Sono-Vigília
/
Tauopatias
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article