A STUDY OF CELL-DEATH IN WERDNIG-HOFFMANN-DISEASE BRAIN

We examined the occurrence of apoptotic cell death in the autopsied br ains of four patients with Werdnig Hoffmann disease (WH), using TdT-me diated DIG-dUTP nick end labeling (TUNEL) and immunohistochemistry for apoptosis-related proteins. Three of the four patients, aged over 6 m onths, exhibited TUNEL-positive cells in the lateral nuclei of the tha lamus, and one of the three patients also had TUNEL-positive cells in the cerebral cortex. The labeled nuclei did not show characteristic fe atures such as nuclear fragmentation or apoptotic bodies, and synaptop hysin-positive granules were observed around some of the TUNEL-positiv e cells, although none of the antibodies against glial markers could v isualize TUNEL-positive cells. TUNEL-positive cells were not observed in other regions examined, including the spinal cord, medulla and cere bellum or in the brains of three age-matched controls. There were neit her immunopositive structures for bcl-2 or p53 nor alteration of in si tu expression of bcl-xs/l or bar in any subject, and the TUNEL-positiv e cells lacked immunopositivity against apoptosis-related proteins. Th e presence of these TUNEL-positive cells might suggest latent neurodeg eneration in the thalamus before central chromatolysis of neurons or n euronal loss appears, although it is not clear whether apoptotic cell death is involved in this degenerative process. (C) 1998 Elsevier Scie nce Ireland Ltd.