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

Item Type:Article
Title:Immune-mediated denervation of the pineal gland underlies sleep disturbance in cardiac disease
Creators Name:Ziegler, K.A. and Ahles, A. and Dueck, A. and Esfandyari, D. and Pichler, P. and Weber, K. and Kotschi, S. and Bartelt, A. and Sinicina, I. and Graw, M. and Leonhardt, H. and Weckbach, L.T. and Massberg, S. and Schifferer, M. and Simons, M. and Hoeher, L. and Luo, J. and Ertürk, A. and Schiattarella, G.G. and Sassi, Y. and Misgeld, T. and Engelhardt, S.
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.
Keywords:Circadian Rhythm, Denervation, Heart Diseases, Melatonin, Pineal Gland, Sleep, Animals, Mice
Publisher:American Association for the Advancement of Science
Page Range:285-290
Date:21 July 2023
Official Publication:https://doi.org/10.1126/science.abn6366
PubMed:View item in PubMed

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