Nutritional regulation of oligodendrocyte differentiation regulates perineuronal net remodeling in the median eminence.

Sara Kohnke ,Michael W Schwartz ,Kimberly M Alonge ,Chao Zhao ,Danaé Nuzzaci ,Takahiro Shimizu ,R J M Franklin ,Ragnhildur Thora Káradóttir ,Wendy B Macklin ,Staffan Holmqvist ,Sophie Buller ,William D Richardson ,Marie A Bentsen ,Brian Lam ,Katherine Ridley ,Hannah A Hathaway ,David H Rowitch ,John Tadross ,Helena Pivoňková ,Hui‐Liang Li ,Giles S.h Yeo ,Clémence Blouet

doi:10.1016/j.celrep.2021.109362

Abstract

SummaryThe mediobasal hypothalamus (MBH; arcuate nucleus of the hypothalamus [ARH] and median eminence [ME]) is a key nutrient sensing site for the production of the complex homeostatic feedback responses required for the maintenance of energy balance. Here, we show that refeeding after an overnight fast rapidly triggers proliferation and differentiation of oligodendrocyte progenitors, leading to the production of new oligodendrocytes in the ME specifically. During this nutritional paradigm, ME perineuronal nets (PNNs), emerging regulators of ARH metabolic functions, are rapidly remodeled, and this process requires myelin regulatory factor (Myrf) in oligodendrocyte progenitors. In genetically obese ob/ob mice, nutritional regulations of ME oligodendrocyte differentiation and PNN remodeling are blunted, and enzymatic digestion of local PNN increases food intake and weight gain. We conclude that MBH PNNs are required for the maintenance of energy balance in lean mice and are remodeled in the adult ME by the nutritional control of oligodendrocyte differentiation.

Highlights

The median eminence (ME) of the mediobasal hypothalamus (MBH) is a bidirectional gateway between the hypothalamus and the periphery, with diverse roles in mammalian physiology and the regulation of neuroendocrine axes
Little is known about how other glial cell types may contribute to these functions, but emerging evidence highlights the unique properties of ME glial populations, in particular oligodendrocyte progenitor cells (OPCs)
ME tanycytes have been proposed to mediate the nutritional regulation of the ME-CSF barrier (Langlet et al, 2013a), but the mechanisms mediating the plasticity of the ME-arcuate nucleus of the hypothalamus (ARH) barrier in response to nutritional cues remain unclear

Summary

Introduction

The median eminence (ME) of the mediobasal hypothalamus (MBH) is a bidirectional gateway between the hypothalamus and the periphery, with diverse roles in mammalian physiology and the regulation of neuroendocrine axes. The ME vasculature lacks a blood-brain barrier (BBB), allowing axons of hypothalamic neuroendocrine neurons to access a BBB-free area when entering the ME and release hypothalamic-releasing hormones into the portal circulation. The ME fenestrated endothelium allows circulating signals to freely diffuse into the ME and adjacent arcuate nucleus of the hypothalamus (ARH), which is rich in neurons critical to appetite regulation and energy balance, giving local neurons privileged access to peripheral signals. The ME-ARH barrier is functionally critical, but its structural components remain unclear (Yoo et al, 2019). Little is known about how other glial cell types may contribute to these functions, but emerging evidence highlights the unique properties of ME glial populations, in particular oligodendrocyte progenitor cells (OPCs). Additional local roles for OPCs may include the modulation of hypothalamic leptin sensing (Djogo et al, 2016; Yasumoto et al, 2018)

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Discussion

Conclusion