A plastic aggrecan barrier modulated by peripheral energy state gates metabolic signal access to arcuate neurons.

Autor: Kuczynski-Noyau L; Univ. Lille, INSERM, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition, UMR-S1172, EGID, Lille, France., Karmann S; Univ. Lille, INSERM, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition, UMR-S1172, EGID, Lille, France., Alberton P; Department for Orthopaedics and Trauma Surgery Musculoskeletal University Center Munich (MUM) University Hospital, LMU, Munich, Germany.; Division of Hand, Plastic and Aesthetic Surgery LMU University Hospital, LMU, Munich, Germany., Martinez-Corral I; Univ. Lille, INSERM, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition, UMR-S1172, EGID, Lille, France., Nampoothiri S; Univ. Lille, INSERM, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition, UMR-S1172, EGID, Lille, France., Sauvé F; Univ. Lille, INSERM, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition, UMR-S1172, EGID, Lille, France., Lhomme T; Univ. Lille, INSERM, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition, UMR-S1172, EGID, Lille, France., Quarta C; Univ. Bordeaux, INSERM, Neurocentre Magendie, U1215, Bordeaux, France., Apte SS; Department of Biomedical Engineering, Cleveland, OH, USA., Bouret S; Univ. Lille, INSERM, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition, UMR-S1172, EGID, Lille, France., Aszodi A; Department for Orthopaedics and Trauma Surgery Musculoskeletal University Center Munich (MUM) University Hospital, LMU, Munich, Germany., Rasika S; Univ. Lille, INSERM, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition, UMR-S1172, EGID, Lille, France., Ciofi P; Univ. Bordeaux, INSERM, Neurocentre Magendie, U1215, Bordeaux, France., Dam J; Institut Cochin, INSERM, CNRS, Université Paris Cité, Paris, France., Prévot V; Univ. Lille, INSERM, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition, UMR-S1172, EGID, Lille, France., Mattot V; Univ. Lille, INSERM, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition, UMR-S1172, EGID, Lille, France. virginie.mattot@inserm.fr.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Aug 07; Vol. 15 (1), pp. 6701. Date of Electronic Publication: 2024 Aug 07.
DOI: 10.1038/s41467-024-50798-9
Abstrakt: The hypothalamic arcuate nucleus (ARH) contains neurons vital for maintaining energy homeostasis that sense and respond to changes in blood-borne metabolic hormones. Despite its juxtaposition to the median eminence (ME), a circumventricular organ lacking a blood-brain barrier and thus exposed to circulating molecules, only a few ventral ARH neurons perceive these extravasating metabolic signals due to a poorly understood ME/ARH diffusion barrier. Here, we show in male mice that aggrecan, a perineural-net proteoglycan deposited by orexigenic ARH neurons, creates a peculiar ventrodorsal diffusion gradient. Fasting enhances aggrecan deposition more dorsally, reinforcing the diffusion barrier, particularly around neurons adjacent to fenestrated capillary loops that enter the ARH. The disruption of aggrecan deposits results in unregulated diffusion of blood-borne molecules into the ARH and impairs food intake. Our findings reveal the molecular nature and plasticity of the ME/ARH diffusion barrier, and indicate its physiological role in hypothalamic metabolic hormone sensing.
(© 2024. The Author(s).)
Databáze: MEDLINE
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