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Publication : Immune-mediated denervation of the pineal gland underlies sleep disturbance in cardiac disease.

First Author  Ziegler KA Year  2023
Journal  Science Volume  381
Issue  6655 Pages  285-290
PubMed ID  37471539 Mgi Jnum  J:338398
Mgi Id  MGI:7512688 Doi  10.1126/science.abn6366
Citation  Ziegler KA, et al. (2023) Immune-mediated denervation of the pineal gland underlies sleep disturbance in cardiac disease. Science 381(6655):285-290
abstractText  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.
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