Detection of Single and Double Strand DNA Breaks during Excitotoxic or Apoptotic Neuronal Cell Death
Excitotoxins have been implicated in a number of neurodegenerative diseases.1,2 These excitatory amino acids can cause neuronal death by several mechanisms, but their effect on the genome is not well defined. Damage of the genomic as well as mitochondrial DNA may appear during chronic excitotoxicity leading to a gradual and progressive accumulation of long term macromolecular damage.3,4 Until now, two major categories of genomic DNA degradation have been distinguished in cells. Apoptotic DNA damage results from a specific molecular and biochemical program mediating a cellular death without the manifestations of cytoplasmic alterations such as swelling and lysosomal activation found in the more commonly described necrotic death.5–7 In most cases, apoptotic cell death involves a specific endonucleic cleavage of double stranded DNA and the cell nuclei adopt a characteristic morphology with fragmentation and perinuclear condensation of chromatin.5,6,8–10 Aside from apoptosis, less specific DNA strand breaks have many possible causes such as radiation,11,12 free radicals and other chemical agents.13–16 Defects in one or more DNA repair enzyme can also lead to the accumulation of DNA damage.17–19
KeywordsCerebellar Granule Cerebellar Granule Cell Nick Translation Glutamate Excitotoxicity Pyknotic Nucleus
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