Immune-mediated denervation of the pineal gland underlies sleep disturbance in cardiac disease.
Science
; 381(6655): 285-290, 2023 07 21.
Article
em En
| MEDLINE
| ID: mdl-37471539
ABSTRACT
Disruption of the physiologic sleep-wake cycle and low melatonin levels frequently accompany cardiac disease, yet the underlying mechanism has remained enigmatic. Immunostaining of sympathetic axons in optically cleared pineal glands from humans and mice with cardiac disease revealed their substantial denervation compared with controls. Spatial, single-cell, nuclear, and bulk RNA sequencing traced this defect back to the superior cervical ganglia (SCG), which responded to cardiac disease with accumulation of inflammatory macrophages, fibrosis, and the selective loss of pineal gland-innervating neurons. Depletion of macrophages in the SCG prevented disease-associated denervation of the pineal gland and restored physiological melatonin secretion. Our data identify the mechanism by which diurnal rhythmicity in cardiac disease is disturbed and suggest a target for therapeutic intervention.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Glândula Pineal
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Ritmo Circadiano
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Gânglio Cervical Superior
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Transtornos do Sono do Ritmo Circadiano
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Cardiopatias
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Macrófagos
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Melatonina
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article