Differential response to lead toxicity in rat primary microglia and astrocytes

Abstract

Lead (Pb) is one of the most widely studied occupational and environmental toxins. Chronic exposure to Pb affects neural function in the central nervous system (CNS). Glial cells in the CNS, such as microglia and astrocytes, respond differently to Pb-induced toxicity. However, the underlying mechanism has not yet been identified. We measured the cell viability and intracellular Pb uptake in rat primary microglia and astrocytes using the CCK-8 assay and inductively coupled plasma mass spectrometry, and found that Pb decreased microglial viability at lower dosages than in astrocytes, while Pb uptake was greater in astrocytes. Pb-induced oxidative stress in microglia results in increased production of reactive oxygen species, down-regulation of glutathione, and enhanced Nrf2 protein expression, while there was no obvious change in astrocytes. The role of Nrf2 in Pb-induced oxidative stress has also been confirmed in primary microglia with the use of Nrf2 small interfering RNA and an Nrf2 agonist. These data indicate that primary microglia were more sensitive to Pb exposure than astrocytes, which is associated with an obvious oxidative stress response and up-regulation of Nrf2 might be involved in this process.