Changes in the distribution of a calcium-dependent ATPase during demyelination and remyelination in the central nervous system

A calcium-adenosine triphosphatase (Ca²⁺-ATPase) activity expressed by CNS nerve fibres has been examined during demyelination and remyelination in rats, 21-26 days after an intraspinal injection of ethidium bromide. The Ca²⁺-ATPase distribution was determined cytochemically, using a technique believed primarily to reflect the presence of ecto-ATPases. We confirm that in normal nerve fibres Ca²⁺-ATPase activity was present on the external surface of the myelin sheath, and on the axolemma at the nodes of Ranvier. Labelling of the internodal axolemma was restricted to small, scattered, punctate regions. However, following demyelination the Ca²⁺-ATPase activity was expressed continuously along both the exposed, previously internodal axolemma of entirely naked axons, and it was particularly prominent at sites of contact between axons and glial-cell processes. During remyelination (which in this lesion is accomplished predominantly by Schwann cells) the proportion of the axonal surface exhibiting Ca²⁺-ATPase activity decreased in concert with the progressive thickening of the new myelin sheath. The non-myelin forming plasmalemma of Schwann cells was positive for the Ca²⁺-ATPase activity, but activity was abruptly lost at the site of compaction between the inner and outer leaflets of the forming myelin sheath. Ecto-ATPase activity is a property of some cell adhesion molecules, and it follows that the changes observed in the distribution of ATPase activity in this study may reflect changes in the axolemma which are important for the successful repair of the lesion by remyelination. The ATPase activity may, for example, reflect the changing distribution of molecules important in aiding axo-glial recognition and the establishment of axo-glial contacts.