Journal Article

DZNE-2023-00737

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Immune-mediated denervation of the pineal gland underlies sleep disturbance in cardiac disease.

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.DZNE* ; Simons, M.DZNE* ; Hoeher, L. ; Luo, J. ; Ertürk, A. ; Schiattarella, G. G. ; Sassi, Y. ; Misgeld, T.DZNE* ; Engelhardt, S.

2023
Assoc. Washington, DC

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Please use a persistent id in citations: doi:10.1126/science.abn6366

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.

Keyword(s): Animals (MeSH) ; Humans (MeSH) ; Mice (MeSH) ; Circadian Rhythm (MeSH) ; Heart Diseases: physiopathology (MeSH) ; Melatonin: metabolism (MeSH) ; Pineal Gland: pathology (MeSH) ; Pineal Gland: physiopathology (MeSH) ; Sleep (MeSH) ; Sleep Disorders, Circadian Rhythm: physiopathology (MeSH) ; Superior Cervical Ganglion: pathology (MeSH) ; Superior Cervical Ganglion: physiopathology (MeSH) ; Macrophages: immunology (MeSH) ; Fibrosis (MeSH) ; Melatonin

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Contributing Institute(s):

1. Neuronal Cell Biology (AG Misgeld)
2. Molecular Neurobiology (AG Simons)

Research Program(s):

1. 351 - Brain Function (POF4-351) (POF4-351)

Appears in the scientific report 2023

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Chemical Reactions ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Current Contents - Physical, Chemical and Earth Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 50 ; Index Chemicus ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

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