Astrocyte survival in the absence of exogenous substrate: Comparison of immature and mature cells

Abstract

Astrocyte cultures prepared from newborn mouse neopallium were grown for either one or three weeks (representing, respectively, immature and mature astrocytes) and then exposed to deprivation of substrate (glucose and amino acids) for up to 48 hr. Cultures which had been deprived of metabolic substrates for either 24, 30, 36 or 48 hr were examined for lactate dehydrogenase efflux into the medium (an indicator of cell death) and ATP content. Significant cell death in mature astrocytes began after 30 hr of incubation in the substrate-deprived medium, a time when ATP had fallen to ∼10% of its initial value. Immature astrocytes survived on a substrate-free medium for 48 hr before there was any indication at all of cell death, and this corresponded to a time when ATP values had fallen to 5% of the initial values. These findings are compared to previous observations during simulated ischemia (substrate deprivation plus anoxia) when (1) there was a faster cell death and (2) cell death occurred at higher ATP levels.