Felipe Correa-da-Silva, Jari B Berkhout, Pim Schouten, Margje Sinnema, Constance T R M Stumpel, Leopold M G Curfs, Charlotte Höybye, Ahmed Mahfouz, Onno C Meijer, Alberto M Pereira, Eric Fliers, Dick F Swaab, Andries Kalsbeek, Chun-Xia Yi
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引用次数: 0
Abstract
The hypothalamic suprachiasmatic nucleus (SCN) hosts the central circadian pacemaker and regulates daily rhythms in physiology and behavior. The SCN is composed of peptidergic neuron populations expressing arginine vasopressin (AVP) and vasoactive intestinal polypeptide (VIP), as well as glial cells. Patients with Prader-Willi Syndrome (PWS) commonly experience circadian disturbances, which are particularly evident in their sleep/wake patterns. Using publicly available single-cell RNA sequencing data, we assessed the cell-type specificity of PWS-causative genes in murine SCN, which revealed the differential presence of PWS-related genes in glial and neural subpopulations. We then investigated neurons and glial cells in the SCN using immunohistochemistry in the postmortem hypothalami of PWS subjects and matched controls. We profiled neural populations characterized by AVP and VIP, astroglia characterized by glial fibrillary acid protein (GFAP), and microglia marked by ionized calcium-binding adapter molecule 1 (Iba1) and NADPH oxidase 2 (NOX2). Our analysis revealed an increased total number, neuronal density, and relative staining intensity of AVP-containing neurons in the PWS compared to controls while VIP-containing cells were unaltered. In contrast, GFAP-expressing astroglial cells were significantly lower in PWS subjects. Moreover, we did not detect any differences in microglia between PWS subjects and controls. Collectively, our findings show that PWS selectively affects AVP-containing neurons and GFAP-expressing astrocytes in the SCN. As each of these cell populations can affect the daily rhythmicity of the SCN biological clock machinery, the disruption of these cells may contribute to the circadian disturbances in patients with PWS.
期刊介绍:
Journal of Neuroendocrinology provides the principal international focus for the newest ideas in classical neuroendocrinology and its expanding interface with the regulation of behavioural, cognitive, developmental, degenerative and metabolic processes. Through the rapid publication of original manuscripts and provocative review articles, it provides essential reading for basic scientists and clinicians researching in this rapidly expanding field.
In determining content, the primary considerations are excellence, relevance and novelty. While Journal of Neuroendocrinology reflects the broad scientific and clinical interests of the BSN membership, the editorial team, led by Professor Julian Mercer, ensures that the journal’s ethos, authorship, content and purpose are those expected of a leading international publication.