A plastic aggrecan barrier modulated by peripheral energy state gates metabolic signal access to arcuate neurons
Nat Commun. 2024-08-07; 15(1):
DOI: 10.1038/s41467-024-50798-9
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Kuczynski-Noyau L(#)(1), Karmann S(#)(1), Alberton P(2)(3), Martinez-Corral
I(1), Nampoothiri S(1), Sauvé F(1), Lhomme T(1), Quarta C(4), Apte SS(5), Bouret
S(1), Aszodi A(2), Rasika S(1), Ciofi P(4), Dam J(6), Prévot V(1), Mattot V(7).
Author information:
(1)Univ. Lille, INSERM, CHU Lille, Laboratory of Development and Plasticity of
the Neuroendocrine Brain, Lille Neuroscience & Cognition, UMR-S1172, EGID,
Lille, France.
(2)Department for Orthopaedics and Trauma Surgery Musculoskeletal University
Center Munich (MUM) University Hospital, LMU, Munich, Germany.
(3)Division of Hand, Plastic and Aesthetic Surgery LMU University Hospital, LMU,
Munich, Germany.
(4)Univ. Bordeaux, INSERM, Neurocentre Magendie, U1215, Bordeaux, France.
(5)Department of Biomedical Engineering, Cleveland, OH, USA.
(6)Institut Cochin, INSERM, CNRS, Université Paris Cité, Paris, France.
(7)Univ. Lille, INSERM, CHU Lille, Laboratory of Development and Plasticity of
the Neuroendocrine Brain, Lille Neuroscience & Cognition, UMR-S1172, EGID,
Lille, France. .
(#)Contributed equally
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).
DOI: 10.1038/s41467-024-50798-9
PMCID: PMC11306556
PMID: 39112471 [Indexed for MEDLINE]
Conflict of interest statement: The authors declare no competing interests.