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

Sara Kohnke, Sophie Buller, Danae Nuzzaci, Katherine Ridley, Brian Lam, Helena Pivonkova, Marie A. Bentsen, Kimberly M. Alonge, Chao Zhao, John Tadross, Staffan Holmqvist, Takahiro Shimizo, Hannah Hathaway, Huiliang Li, Wendy Macklin, Michael W. Schwartz, William D. Richardson, Giles S.H. Yeo, Robin J.M. Franklin, Ragnhildur Þóra KáradóttirDavid H. Rowitch, Clemence Blouet*

*Corresponding author for this work

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Abstract

The 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.

Original languageEnglish
Article number109362
Pages (from-to)109362
JournalCell Reports
Volume36
Issue number2
DOIs
Publication statusPublished - 13 Jul 2021

Bibliographical note

Publisher Copyright:
© 2021 The Authors

We thank the Flow Cytometry Core of the Cambridge Institute of Medical Research; the histopathology, imaging, and disease model cores at the Wellcome Trust-MRC Institute of Metabolic Science; the Light Microscopy Core at the Cancer Research UK Cambridge Institute; and Cambridge Brain Bank (CBB) for providing brain tissue for this study. This work was supported by the MRC (MR/S011552/1; C.B.), a Wellcome Trust PhD Programme (108926/B/15/Z; S.B.), the BBSRC DTP program (S.K.), the ERC (no. 771411; R.T.K.), the Wellcome Pathfinder Award (204488/Z/16/Z; R.T.K. and H.P.), the MRC MDU, the Wellcome Trust Strategic award for the MRL Disease Model Core and Imaging facilities (MRC_MC_UU_12012/5, 100574/Z/12/Z, MRC_MC_UU_00014/5, 208363/Z/17/Z), the Adelson Medical Research Foundation (R.J.M.F. and D.H.R.), the UK MS Society (R.J.M.F. and C.Z.), and the l’Oreal-UNESCO For Women In Science program. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. This work is licensed under a Creative Commons Attribution 4.0 International License.

Other keywords

  • energy balance
  • glucose homeostasis
  • hypothalamus
  • median eminence
  • nutrition
  • obesity
  • oligodendrocyte
  • perineuronal nets
  • plasticity

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