Chromatin condensation during glutamate-induced excitotoxicity of cerebellar [correction of celebellar] granule neurons precedes disintegration of nuclear DNA into high molecular weight DNA fragments.

The disturbance of the intracellular ionic homeostasis after activation of channel-associated membrane receptors by the excitatory neurotransmitters represents a principle event that triggers excitotoxic cell death of neurons. Here we demonstrate that glutamate-induced excitotoxicity of cerebellar granule neurons was accompanied by apoptosis-like nuclear shrinkage, chromatin condensation, and disintegration of nuclear DNA into high molecular weight DNA fragments, but was neither associated with activation of caspase 1, -2, -3, -9, nor was protected by a pan-caspase inhibitor, zVAD-fmk. We further demonstrate that chromatin condensation took place at the early stages of excitotoxicity and preceded nuclear DNA fragmentation. The results suggest that fragmentation of nuclear DNA and condensation of chromatin are uncoupled events during neuronal cell death