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N E U R O N G L I A I N T E R AC T I O N S O P I N I O N
Myelination and the trophic support of long axons
Klaus-Armin Nave
Abstract | In addition to their role in providing myelin for rapid impulse propagation, the glia that ensheath long axons are required for the maintenance of normal axon transport and long-term survival. This presumably ancestral function seems to be independent of myelin membrane wrapping. Here, I propose that ensheathing glia provide trophic support to axons that are metabolically isolated, and that myelin itself might cause such isolation. This glial support of axonal integrity may be relevant for a number of neurological and psychiatric diseases.
The interaction of neurons and glia is a feature of virtually all nervous systems. As brains have become larger during vertebrate evolution, the proportion of brain cells that are glia has increased1. The oligodendrocytes of the CNS and the Schwann cells of thePNS are best known for making the myelin that ensheaths neuronal axons. The neurodegenerative phenotypes of mouse strains that carry mutations affecting these specialized glia have revealed that the ensheathing cells are essential not only for myelin assembly but also for the functional integrity and longterm survival of axons25. This requirement is also reflected in the axonal degeneration observed in human neurological diseases in which glial support fails.
The evolution of myelin (BOX 1) reduced
the energy required for neuronal communication and boosted the speed of impulse propagation, allowing complex nervous systems to operate quickly and efficiently6.
However, the myelin sheath itself could be a doubleedged sword. The nearly complete insulation of axons by myelin restricts their access to extracellular metabolic substrates. In this Perspective, I combine observations that have emerged from the analysis of mouse mutants carrying gliaspecific defects with those of the pathology of human myelin diseases into a larger picture of unrecognized glial functions. These data suggestthat oligodendrocytes (which are coupled
to astrocytes) and Schwann cells preserve fast axonal transport and longterm axonal integrity in the nervous system. More speculatively, I propose that long axonal tracts depend on these glia to meet the metabolic demands and energy requirements of rapid impulse propagation and axonal transport.
Myelin in...