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Ziegler, K.A.* ; Ahles, A.* ; Dueck, A.* ; Esfandyari, D.* ; Pichler, P.* ; Weber, K.* ; Kotschi, S.* ; Bartelt, A. ; Sinicina, I.* ; Graw, M.* ; Leonhardt, H.* ; Weckbach, L.T.* ; Massberg, S.* ; Schifferer, M.* ; Simons, M.* ; Höher, L. ; Luo ; Ertürk, A. ; Schiattarella, G.G.* ; Sassi, Y.* ; Misgeld, T.* ; Engelhardt, S.*

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

Science 381, 285-290 (2023)

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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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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Superior Cervical-ganglion; Expression; Transgene; Melatonin; Neurons; Atrial

ISSN (print) / ISBN 0036-8075

e-ISSN 1095-9203

Journal Science

Quellenangaben Volume: 381, Issue: 6655, Pages: 285-290

Publisher American Association for the Advancement of Science (AAAS)

Publishing Place 1200 New York Ave, Nw, Washington, Dc 20005 Usa

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Diabetes and Cancer (IDC)
Institute for Tissue Engineering and Regenerative Medicine (ITERM)

Grants TUM
European Research Council
Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)
DZHK (German Centre for Cardiovascular Research)
DFG
German Cardiac Society
Munich Center for Systems Neurology
ERC under the European Union
German Center for Neurodegenerative Diseases (DZNE)
BMBF