Streptozotocin toxicity in vitro depends on maturity of neurons.

Streptozotocin (STZ) is a glucosamine-nitrosourea compound that is particularly toxic to the insulin-producing beta-cells of the pancreas in mammals; it is used for experimental simulation of sporadic Alzheimer's disease by means of intracerebroventricular administration in vivo. Here we show that the application of 3-4 mM STZ to primary culture for 48 h induces neuronal death in immature (2-3 days in vitro) cultures of rat cerebellar granule cells. Mature cultures (7-8 days in vitro) were poorly sensitive to this toxic treatment. Immature cultures demonstrated a high expression of the protein PSA-NCAM, the marker of immature neurons, and they were insensitive to the toxic effect of glutamate. In mature cultures, this protein was poorly expressed, whereas neurons showed a very high sensitivity to the toxic effect of glutamate. Measurements of the concentration of intracellular free calcium ions ([Ca2+]i) showed that the STZ-induced [Ca2+]i increase in young neurons was six times higher than that in mature neurons. Our results show that STZ is very toxic for immature neurons and probably it can significantly impair neurogenesis.