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

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...

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Autores principales: Dong, Qing, Ptáček, Louis J., Fu, Ying-Hui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10104526/
https://www.ncbi.nlm.nih.gov/pubmed/37014857
http://dx.doi.org/10.1073/pnas.2221686120
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author Dong, Qing
Ptáček, Louis J.
Fu, Ying-Hui
author_facet Dong, Qing
Ptáček, Louis J.
Fu, Ying-Hui
author_sort Dong, Qing
collection PubMed
description 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.
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spelling pubmed-101045262023-04-15 Mutant β(1)-adrenergic receptor improves REM sleep and ameliorates tau accumulation in a mouse model of tauopathy Dong, Qing Ptáček, Louis J. Fu, Ying-Hui Proc Natl Acad Sci U S A Biological Sciences 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. National Academy of Sciences 2023-04-04 2023-04-11 /pmc/articles/PMC10104526/ /pubmed/37014857 http://dx.doi.org/10.1073/pnas.2221686120 Text en Copyright © 2023 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by/4.0/This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Biological Sciences
Dong, Qing
Ptáček, Louis J.
Fu, Ying-Hui
Mutant β(1)-adrenergic receptor improves REM sleep and ameliorates tau accumulation in a mouse model of tauopathy
title Mutant β(1)-adrenergic receptor improves REM sleep and ameliorates tau accumulation in a mouse model of tauopathy
title_full Mutant β(1)-adrenergic receptor improves REM sleep and ameliorates tau accumulation in a mouse model of tauopathy
title_fullStr Mutant β(1)-adrenergic receptor improves REM sleep and ameliorates tau accumulation in a mouse model of tauopathy
title_full_unstemmed Mutant β(1)-adrenergic receptor improves REM sleep and ameliorates tau accumulation in a mouse model of tauopathy
title_short Mutant β(1)-adrenergic receptor improves REM sleep and ameliorates tau accumulation in a mouse model of tauopathy
title_sort mutant β(1)-adrenergic receptor improves rem sleep and ameliorates tau accumulation in a mouse model of tauopathy
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10104526/
https://www.ncbi.nlm.nih.gov/pubmed/37014857
http://dx.doi.org/10.1073/pnas.2221686120
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