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Review
, 145 (4), 1426-38

Neurotransmitter Receptors in the Life and Death of Oligodendrocytes

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Review

Neurotransmitter Receptors in the Life and Death of Oligodendrocytes

R Káradóttir et al. Neuroscience.

Abstract

Oligodendrocytes are crucial to the function of the mammalian brain: they increase the action potential conduction speed for a given axon diameter and thus facilitate the rapid flow of information between different brain areas. The proliferation and differentiation of developing oligodendrocytes, and their myelination of axons, are partly controlled by neurotransmitters. In addition, in models of conditions like stroke, periventricular leukomalacia leading to cerebral palsy, spinal cord injury and multiple sclerosis, oligodendrocytes are damaged by glutamate and, contrary to dogma, it has recently been discovered that this damage is mediated in part by N-methyl-D-aspartate receptors. Mutations in oligodendrocyte neurotransmitter receptors or their interacting proteins may cause defects in CNS function. Here we review the roles of neurotransmitter receptors in the normal function, and malfunction in pathological conditions, of oligodendrocytes.

Figures

Fig. 1
Fig. 1
Spatial segregation of NMDA and AMPA/kainate receptors in myelinating oligodendrocytes. AMPA/kainate receptors (blue) are preferentially located on the soma, while NMDA receptors (yellow) are preferentially located on the myelinating processes, although this segregation is not absolute. Cutaway of myelin shows that NMDA receptors are found in the outer myelin wrap (o), the inner wrap (i) nearest the axon, and also deep in the compact myelin (m). This schematic diagram of the myelin ignores the fact that the oligodendrocyte cytoplasm is, in reality, thicker in the innermost and outermost turns of the myelin.
Fig. 2
Fig. 2
Control of oligodendrocyte development by neurotransmitters. Black arrows show the progression of oligodendrocytes from precursors, which migrate and proliferate, through immature oligodendrocytes, which send out processes seeking axons to myelinate, to mature myelinating oligodendrocytes that form myelin sheaths. Blue arrows show positive effects of neurotransmitters; red arrows show inhibitory effects. Glutamate and ATP are released (green) from active axons. Glutamate is released by exocytosis onto oligodendrocyte precursors, and by reversed uptake onto mature cells. The mechanism of release of ATP is uncertain. ATP is converted to adenosine by extracellular ATPases. ATP also induces astrocytes to release leukemia inhibitory factor (LIF). GABA is also released by exocytosis onto precursors; the origins and release mechanisms for ACh and dopamine are unknown.
Fig. 3
Fig. 3
Receptor distribution defines the spatial segregation of damage expected when glutamate (glu) is released from axons and oligodendrocytes by reversal of uptake carriers (orange) in conditions of energy deprivation. Glutamate released from axons will activate NMDA receptors (yellow) on the inner wrap (i) of the myelin, leading to ion flux into the myelin and myelin damage. Glutamate released from oligodendrocytes will activate AMPA/kainate receptors (blue) on the soma (possibly leading to death of the soma) and also NMDA receptors on the inner and outer (o) wraps of the myelin.

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