Science (New York, N.Y.) · 2023
Immune-mediated denervation of the pineal gland underlies sleep disturbance in cardiac disease.
СтатьяНазвание и аннотация: Перевод в очереди
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Ziegler Karin A, Ahles Andrea, Dueck Anne, Esfandyari Dena, Pichler Pauline, Weber Karolin, Kotschi Stefan, Bartelt Alexander, Sinicina Inga, Graw Matthias, Leonhardt Heinrich, Weckbach Ludwig T, Massberg Steffen, Schifferer Martina, Simons Mikael, Hoeher Luciano, Luo Jie, Ertürk Ali, Schiattarella Gabriele G, Sassi Yassine, Misgeld Thomas, Engelhardt Stefan
Аннотация
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.