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  • Title: Apoptotic positive cells in Krabbe brain and induction of apoptosis in rat C6 glial cells by psychosine.
    Author: Jatana M, Giri S, Singh AK.
    Journal: Neurosci Lett; 2002 Sep 20; 330(2):183-7. PubMed ID: 12231442.
    Abstract:
    Globoid cell leukodystrophy (GLD) is an autosomal recessive disorder of infants, caused by deficient activity of cerebroside-beta-galactosidase resulting in loss of myelin accompanied by loss of oligodendrocytes. The loss of oligodendrocyte population is accompanied by accumulation of psychosine, which is considered as the molecule responsible for the observed pathophysiology of GLD. We were able to detect apoptotic cells by terminal dUTP nick-end labeling assay and nuclear localization of p53 in postmortem brain tissue of Krabbe's disease patients, which were not detected in the control brain. To study the role of psychosine in cell death, we investigated the effect of psychosine on C6 glial cell survival by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Similar to ceramide (43.8% loss) the galactopsychosine and glucopsychosine treatment killed up to 46.3 and 48.75% of cells, respectively. On the other hand, sphingosine had no effect. DNA laddering assay confirmed these results. Moreover, psychosine-induced detection of annexin-V positive cells supports a role for psychosine in C6 glial cell death via the apoptotic pathway. These results indicate that psychosine may play a role in apoptotic cell loss observed in GLD brain.
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