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Imbalanced innervation of the hypothalamic paraventricular nucleus by the AgRP and α-MSH axonal projections in germ-free mice.

Oarii Vahirua,Mouna El Mehdi,E. Lahaye,Aurélie Balvay,Sylvie Rabot,Sergueï O. Fetissov

Published 2025 in Developmental Neuroscience

ABSTRACT

INTRODUCTION Innervation of the paraventricular nucleus of the hypothalamus (PVN) by the orexigenic agouti-related protein (AgRP) and anorexigenic α-melanocyte-stimulating hormone (α-MSH) neurons of the arcuate nucleus (ARC) is a key element in the appetite-regulating neuronal circuitry whose development is influenced by circulating metabolic signals. In the present work, we studied if PVN innervation by the AgRP and α-MSH fibers is influenced by gut microbiota. METHODS To this aim, we compared, using immunohistochemistry, the innervation of PVN by AgRP and α-MSH fibers between germ-free and specific pathogen-free 7-week-old female mice. RESULTS We found that germ-free mice display an increased innervation of the PVN by both AgRP and α-MSH fibers, but also that the increase in AgRP fiber density was about twice as pronounced as that of α-MSH. CONCLUSION These data reveal that gut microbiota plays a modulatory role in the development of the ARC/PVN axonal projections. An imbalance between AgRP and α-MSH innervation in germ-free mice may contribute to their metabolic and behavioral alterations.

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