DNA FRAGMENTATION AND IMMEDIATE-EARLY GENE-EXPRESSION IN RAT STRIATUMFOLLOWING QUINOLINIC ACID ADMINISTRATION

Excitotoxic cell death is hypothesized to contribute to numerous neuro pathologic conditions, including hypoxic/ischemic encephalopathy, hypo glycemia, Parkinson's disease, and Huntington's disease. Neuronal deat h from excitotoxic lesions has been shown to be an active process, wit h activation of immediate early gene transcription, resulting in secon dary changes in gene expression. Another feature of neurotoxic cell de ath that has been examined is the presence of DNA fragmentation, which presumably indicates impending nuclear disintegration. A technique ha s been described for labeling fragmented DNA in situ, allowing precise determination of the anatomic and temporal distribution of neurons af ter an excitotoxic lesion. To investigate this phenomenon, we performe d in situ nick translation on brain tissue from rats that have undergo ne stereotaxically placed intrastriatal quinolinic acid injections. Fu rthermore, in these same animals we analyzed the expression of c-fos m RNA to compare the time course and regional distribution of DNA fragme ntation with immediate early gene activation after an excitotoxic lesi on. Our analysis indicates that c-fos expression increases soon after quinolinic acid injection, is widespread in rat brain, but is effectiv ely absent by 24 h postinjection. DNA fragmentation, however, is limit ed to striatum and is maximal at 24 h after injection. These results d emonstrate the sensitivity of in situ nick translation for the detecti on of regional neuropathology and illustrate the temporal and spatial relationship of c-fos expression to excitotoxic neuronal death. (C) 19 95 Academic Press, Inc.