Roles of Glial Cells for Neurodegeneration in Prion Diseases

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It is unknown how affects Amphotericin B (AmB), reported to be a therapeutic drug against prion diseases, on microglial function. Cultured microglia prepared from rat new-born brain were stimulated to produce nitric oxide (NO) by prion peptide (106-126) (PrP), and also by AmB. The level of the NO production stimulated by AmB was enhanced by the presence of the PrP. These results suggest a certain interaction between AmB and PrP and the interaction modulates the microglial cell function. The elucidation of this interaction might be a key for the therapeutic mechanism of AmB against prion diseases.The physiological functions of prion protein is speculative; however, it is suggested that prion protein is involves in the, mechanism of Cu transport, which is an essential metal for superoxide dismutase (SOD), through cell membrane. We have established the method for the measurement of extracellular SOD (EC-SOD) activity in the living cells. The activities of EC-SOD of cultured astrocytes from rat embryo's brain decreased to a half after stimulation by lipopolysaccharide (LPS) for 24 hr, whereas the intracellular SODs (cytoplasmic and mitochondrial) increased. On the other hand, the activity of SOD in the culture medium increased by LPS dose-dependently. These results suggest that EC-SOD is released from cell surface into the medium. Astrocytes may play an important role for the regulation of brain parenchymal level of active oxygen species by changing localization of EC-SOD ; protecting surrounding neurons from oxidative stress.