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Oligodendrocytes of the adult median eminence



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Buller, Sophie 


Oligodendrocytes (OLs) are the myelin forming cells of the CNS. Once thought to be generated exclusively during development, recent advances have shown that new OLs are generated in the adult brain from oligodendrocyte progenitor cells (OPCs) in response to physiologically relevant stimuli such as motor skill learning. Emerging evidence suggests that OL genesis is influenced by nutritional stimuli in the healthy and diseased brain, with recent studies highlighting that OPCs in the adult median eminence (ME) are highly proliferative and rapidly differentiate in response to nutritional signals. As such, these data raise questions about new OL and myelin generation in the ME at baseline, the fate of pre-existing OLs here, and the functional significance of OLs generated in the healthy adult ME given its diverse roles in the regulation of energy balance, glucose homeostasis, and neuroendocrine function. Data presented in this thesis demonstrate that in contrast to the corpus callosum (a well- characterised white matter tract), new myelin forming OLs are generated at a high rate and rapidly turnover in the healthy adult ME, which results in the appearance of relatively stable population of OLs in the ME over time in adult mice. Examining the impact of metabolic state on these processes revealed nutritional regulation of the ME OL lineage. Diet induced obesity, for example, blunts OL generation and turnover and increases ME myelin amounts, whereas caloric restriction reduces ME OPC differentiation and myelination. Intriguingly, blocking new OL generation in the adult brain using Pdgfrα-Cre/ERT2;Rosa26-YFP;Myrffl/fl mice mimics key metabolic and neuroendocrine adaptations to energy deficit, and is associated with cellular and structural remodelling of the ME, resulting in increased ME-arcuate nucleus (ARC) barrier permeability. Exploring potential mechanisms regulating OL lineage plasticity revealed that myelin debris generated during myelin turnover recruits immune cells to the ME, which are required for ongoing OL plasticity and, together with newly formed OLs, may contribute towards local perineuronal net remodelling. Collectively these observations indicate that 1) OL lineage cells are highly plastic and sense, adapt, and respond to nutritional stimuli, 2) ME OL plasticity plays a physiological role in the adaptative responses to states of negative energy balance, 3) ME OL plasticity is required for physiological hypothalamic functions via regulating the access of circulating factors to key hypothalamic feeding centres and 4) microglia contribute towards ME OL lineage plasticity and function, implicating a novel role for microglia in health.





Blouet, Clemence


Hypothalamus, Median eminence, Metabolism, Myelin, Neuroendocrinology, Neuroplasticity, Oligodendrocyte


Doctor of Philosophy (PhD)

Awarding Institution

University of Cambridge