Inosine is a
purine nucleoside and is considered protective to neural cells including neurons and astrocytes against hypoxic injury. However, whether oligodendrocytes (OLs) could also be protected from
hypoxia by
inosine is not known. Here we investigated the effects of
inosine on primarily cultured rat OLs injured by
rotenone-mediated chemical
hypoxia, and the mechanisms of the effects using
ATP assay, MTT assay, PI-Hoechst staining, TUNEL, and immunocytochemistry. Results showed that
rotenone exposure for 24 h caused cell death and impaired viability in both immature and mature OLs, while pretreatment of 10 mM
inosine 30 min before
rotenone administration significantly reduced cell death and improved the viability of OLs. The same concentration of
inosine given 120 min after
rotenone exposure also improved viability of injured mature OLs. Immunocytochemistry for
nitrotyrosine and cellular
ATP content examination indicated that
inosine may protect OLs by providing
ATP and scavenging
peroxynitrite for cells. In addition, immature OLs were more susceptible to
hypoxia than mature OLs; and at the similar degree of injury,
inosine protected immature and mature OLs differently. Quantitative real-time PCR revealed that expression of
adenosine receptors was different between these two stages of OLs. These data suggest that
inosine protect OLs from hypoxic injury as an
antioxidant and
ATP provider, and the protective effects of
inosine on OLs vary with cell differentiation, possibly due to the
adenosine receptors expression profile. As OLs form myelin in the central nervous system,
inosine could be used as a promising
drug to treat
demyelination-involved disorders.