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Neurotoxicity of psychosine in neural cell cultures: The pathogenesis of Krabbe's disease


, : Neurotoxicity of psychosine in neural cell cultures: The pathogenesis of Krabbe's disease. Jikeikai Medical Journal 40(2): 171-179

In order to understand the possible cause of demyelination in Krabbe's globoid cell leukodystrophy, the neurotoxicity of psychosine (galactosylsphingosine) in neural cell culture of mouse and human was investigated. The psychosine concentration necessary to cause damage to the cell cultures was approximately 12.5 nmol/ml. Under a phase contrast microscopic examination, inhibition of processes growth, desquamation of cultured cells, and degeneration of processes were observed. By immunofluorescence staining method using an anti-neurofilament antibody, psychosine treated cells showed destruction of cytoskeleton and pathy intracellular changes. An electron microscopic study showed swelling of mitochondria, disruption of cristae in mitochondria, and disappearance of microtubules and neuro-filaments. These data suggest that psychosine influences mitochondrial function, possibly through inhibition of oxidative phosphorylation, and hence results in the destruction of cellular components.

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