Nutritional regulation of oligodendrocyte differentiation regulates perineuronal net remodeling in the median eminence.
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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.
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2211-1247
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Medical Research Council (MC_UU_12012/1)
Medical Research Council (MC_UU_12012/5)
Wellcome Trust (204845/Z/16/Z)
Medical Research Council (MR/S011552/1)
Wellcome Trust (204488/Z/16/Z)
Wellcome Trust (108926/B/15/Z)
Wellcome Trust (208363/Z/17/Z)
European Research Council (771411)
MRC (MC_UU_00014/5)
Medical Research Council (MC_PC_17230)
MRC (MR/S026193/1)
MRC (MC_UU_00014/1)
Biotechnology and Biological Sciences Research Council (BB/S017593/1)
Medical Research Council (MC_PC_12012)