A study of cell death in Werdnig Hoffmann disease brain.

We examined the occurrence of apoptotic cell death in the autopsied brains of four patients with Werdnig Hoffmann disease (WH), using TdT-mediated DIG-dUTP nick end labeling (TUNEL) and immunohistochemistry for apoptosis-related proteins. Three of the four patients, aged over 6 months, exhibited TUNEL-positive cells in the lateral nuclei of the thalamus, and one of the three patients also had TUNEL-positive cells in the cerebral cortex. The labeled nuclei did not show characteristic features such as nuclear fragmentation or apoptotic bodies, and synaptophysin-positive granules were observed around some of the TUNEL-positive cells, although none of the antibodies against glial markers could visualize TUNEL-positive cells. TUNEL-positive cells were not observed in other regions examined, including the spinal cord, medulla and cerebellum or in the brains of three age-matched controls. There were neither immunopositive structures for bcl-2 or p53 nor alteration of in situ expression of bcl-xs/l or bax in any subject, and the TUNEL-positive cells lacked immunopositivity against apoptosis-related proteins. The presence of these TUNEL-positive cells might suggest latent neurodegeneration in the thalamus before central chromatolysis of neurons or neuronal loss appears, although it is not clear whether apoptotic cell death is involved in this degenerative process.