Lamin and beta-tubulin fragmentation precede chromatin degradation in glutamate-induced neuronal apoptosis.

Abstract

During ischaemic brain injury, glutamate accumulation with overstimulation of postsynaptic glutamate receptors and intracellular Ca2+ overload lead to neuronal death. We have shown previously that delayed neuronal death in cultures of cerebellar granule cells (CGCs) exposed to glutamate occurs by apoptosis. Here, we report that lamin cleavage and dissolution of the microtubule network precede chromatin fragmentation in glutamate-induced CGC apoptosis. Like other events that characterize excitotoxic cell death, degradation of lamins, beta-tubulin and disruption of microtubule architecture is inhibited by the NMDA-receptor antagonist MK-801. Our findings suggest that cleavage of key cytoskeletal elements is an important step in glutamate-induced neuronal apoptosis.