Rapid Communication: Oxidative Stress Induces Apoptosis in Embryonic Cortical Neurons

TLDR

Glutamate‑induced glutathione depletion in immature embryonic cortical neurons causes oxidative stress and cell death. The study aims to investigate how free radicals trigger neuronal degeneration. An in‑vitro model of glutamate‑induced glutathione depletion in embryonic cortical neurons was used to examine the underlying mechanisms. Glutathione depletion induces chromatin hypercondensation, fragmentation, DNA laddering, and apoptotic morphology, all of which are prevented by antioxidants and inhibitors of macromolecular synthesis, demonstrating that oxidative stress induces apoptosis in neurons.

Abstract

Abstract: Glutamate‐induced glutathione depletion in immature embryonic cortical neurons has been shown to lead to oxidative stress and cell death. We have used this in vitro model to investigate the mechanism(s) by which free radicals induce neuronal degeneration. We find that glutathione depletion leads to hypercondensation and fragmentation of chromatin into spherical or irregular shapes, a morphologic signature of apoptosis. These morphologic changes are accompanied by laddering of DNA into multiple oligonucleosomal fragments and can be prevented by the antioxidants idebenone and butylated hydroxyanisole. Cell death induced by glutathione depletion can also be prevented by inhibitors of macromolecular synthesis. Taken together, these observations suggest that oxidative stress can induce apoptosis in neurons.