Effects of psychosine (galactosylsphingosine) on the survival and the fine structure of cultured Schwann cells.
The cytotoxicity of psychosine (galactosylsphingosine) for cultured rat Schwann cells was studied by maintaining them in medium containing 1, 10, 50, 75 and 100 microM psychosine for 24, 48 and 72 hours (h). When incubated in 50-100 microM concentrations of psychosine for 24 h, 52-99% of cultured Schwann cells did not survive. Lower concentrations (1-10 microM) did not significantly reduce Schwann cell numbers for the first 24 h. However, only 43-69% of cultured Schwann cells survived in these low concentrations for 48 h, and substantially fewer remained after 72 h of incubation. During incubations in psychosine, bipolar processes of Schwann cells retracted; the resulting oval and rounded Schwann cells still were S-100 positive. When these Schwann cells were transferred into normal medium, their processes elongated quickly. When examined with the electron microscope, the cytoplasm of Schwann cells incubated in psychosine contained numerous membranous inclusions and fewer mitochondria, some of which were swollen. There also were fewer profiles of granular endoplasmic reticulum and some had widely dilated cisternae. These results suggest that 1) exogenous psychosine in concentrations of 1 microM and greater is cytotoxic for cultured rat Schwann cells; 2) psychosine has reversible toxic effects and its turnover is rapid; and 3) psychosine produces membranous inclusions and abnormalities in the mitochondria and granular endoplasmic reticulum of cultured Schwann cells. Our findings support the hypothesis that the accumulation of psychosine in human and murine globoid cell leukodystrophy is toxic for Schwann cells, produces changes in their capacity to maintain myelin, and leads to Schwann cell dysfunction.
Tanaka
K
K
Laboratory of Experimental Neuropathology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892.
Webster
H D
HD
D000818:Animals; D000831:Animals, Newborn; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D007700:Kinetics; D008854:Microscopy, Electron; D008928:Mitochondria / Q000187:drug effects / Q000648:ultrastructure; D011609:Psychosine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D009418:S100 Proteins / Q000032:analysis; D012583:Schwann Cells / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D012584:Sciatic Nerve / Q000166:cytology*; D013997:Time Factors
D009418:S100 Proteins; D011609:Psychosine