Myelin – much more than a mere axonal insulator.

In the central nervous system, the majority of axons are surrounded by a myelin sheath. Myelin almost completely encases the axon, and in so doing, shields it from the extracellular milieu. While this facilitates rapid conduction of electrical impulses, it seems liable to limit the axon’s access to glucose. This raises the question as to how axonal ATP synthesis is fueled, particularly in long axons that are remote from their neuronal cell body. We and others have provided evidence for the possibility that oligodendrocytes locally supply lactate to the underlying axon to fuel oxidative phosphorylation in axonal mitochondria (Funfschilling et al., 2012;Lee et al., 2012).

The non-compact myelin or ‘myelinic channel’ provides a route through which oligodendroglial products could reach the axon. To examine the structure and function of the ‘myelinic channel’, we used immunocytochemistry and time-lapse imaging of CNS myelinating cultures from Cnp-mEos2-PTS1::PLP1-CreERT2::Rosa26 TandemDimer(TD)Tomatoflox/+ mouse embryos (E13), in which the myelinic channel and oligodendroglial peroxisomes are fluorescently labelled. Cultures were treated with inflammatory factors or modulators of neural activity and the consequences for the myelinic channel and its organelles were examined.

I will present the preliminary results of these studies.