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The acid instability of myelin. A model for myelin degeneration in multiple sclerosis
P R Young1, W R Snyder, D A Vacante
1Department of Chemistry, University of Illinois at Chicago 60680.
Abstract:
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.
Insights
Acidic conditions disrupt myelin in the central nervous system (CNS). This suggests that high lactic acid levels (hyperlactemia) may drive inflammatory demyelination, offering a potential therapeutic target for multiple sclerosis.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Myelin lamellae in the central nervous system (CNS) are crucial for nerve function.
- Inflammatory demyelination is a hallmark of diseases like multiple sclerosis.
- The role of microenvironmental acidity in myelin damage is not fully understood.
Purpose of the Study:
- To investigate the effect of acidic conditions on myelin structure.
- To explore the link between lactic acid production by macrophages and myelin damage.
- To identify potential therapeutic strategies for demyelinating diseases.
Main Methods:
- Electron microscopy was used to examine bovine spinal cord tissue exposed to varying pH levels.
- Rat peritoneal macrophages were cultured with bovine CNS material to assess lactic acid secretion.
- Micrographs analyzed myelin lamellae integrity under different conditions.
Main Results:
- Acidification (pH 5.5) caused significant vesicular disruption of myelin lamellae.
- Control samples at neutral pH (7.0) exhibited normal, compact myelin.
- Macrophages secreted lactic acid, acidifying the culture medium and damaging myelin.
- Myelin lamellae demonstrated high sensitivity to acidic microenvironments.
Conclusions:
- Local hyperlactemia and decreased interstitial pH are implicated in inflammatory demyelination.
- Acidic microenvironments are detrimental to myelin integrity.
- Antihyperlactic agents may offer a novel therapeutic approach for demyelinating disorders.
- This research provides insights into the pathology of multiple sclerosis and related CNS conditions.