DNA END LABELING (TUNEL) IN HUNTINGTONS-DISEASE AND OTHER NEUROPATHOLOGICAL CONDITIONS

Deoxyribonucleic acid of cells undergoing apoptosis is cleaved by a ca lcium-dependent endonuclease into oligonucleosomal-sized fragments. Th ese fragments can be labeled using the enzyme terminal deoxynucleotidy l transferase so that the cells can be visualized immunohistochemicall y. Few investigators have evaluated this method in disease processes o f the human central nervous system. The Tdt-mediated dUTP-biotin nick end labeling (TUNEL) technique has been investigated in preliminary st udies of a variety of pathologic conditions of the human brain (e.g., gliomas, traumatic brain injury, Parkinson's disease, Parkinson's-Alzh eimer's complex, multisystem atrophy, striatonigral degeneration). We focus, however, on Huntington's disease (HD) because of the availabili ty of well-characterized pathological stages for study, and also becau se of the neurodegenerative diseases studied to date, only Huntington' s disease revealed significant and consistent labeling with this metho d. This implies a possibly unique nature to the mechanism of cell deat h in Huntington's disease compared to the other neurodegenerative dise ases studied. TUNEL+ neurons were found in Grade 1-4 HD neostriatum, w hile labeled astrocytes were found predominantly in the Grade 1 and 2 cases studied to date. TUNEL+ cells were also found in glioblastoma mu ltiforme and traumatic brain injury. We conclude that while there appe ar to be several limitations associated with this technique, it may be useful for identifying both apoptosis and necrosis in certain neuropa thological conditions. (C) 1995 Academic Press, Inc.