The acid instability of myelin. A model for myelin degeneration in multiple sclerosis.
Electron micrographs of samples of bovine spinal cord which have been briefly acidified (10 mM lactate buffer, pH 5.5, 25 degrees C, 15 minutes) prior to being fixed for EM examination, reveal extensive vesicular disruption of the myelin lamellae; micrographs of control samples incubated under identical conditions at pH 7.0, show normal compact lamellae. Culture of thioglycollate-elicited rat peritoneal macrophages in the presence of derivatized, non-ingestible, bovine CNS material results in the secretion of lactic acid and the acidification of the culture medium to levels which are comparable to those which cause lamellae disruption in the tissue slices. Because of the sensitivity of the myelin lamellae to an acidic microenvironment, it is suggested that a local hyperlactemia, with the resulting decrease in interstitial pH, may be a major pathological process in cell-mediated inflammatory demyelination. Antihyperlactemics may therefore provide a new therapeutic approach to minimizing myelin degeneration in multiple sclerosis and in other CNS disorders characterized by inflammatory demyelination.
Young
P R
PR
Department of Chemistry, University of Illinois at Chicago 60680.
Snyder
W R
WR
Vacante
D A
DA
Waickus
C M
CM
Zygas
A P
AP
Grynspan
F
F
Karunatilake
C
C
Wilson
D H
DH
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D006863:Hydrogen-Ion Concentration; D007773:Lactates / Q000378:metabolism*; D019344:Lactic Acid; D008264:Macrophages / Q000378:metabolism; D009103:Multiple Sclerosis / Q000378:metabolism / Q000473:pathology*; D009186:Myelin Sheath / Q000378:metabolism / Q000648:ultrastructure*; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000648:ultrastructure
D007773:Lactates; D019344:Lactic Acid