Doug Strand

Publication Date

Spring 2001


School of Behavioral Sciences




The fundamental mechanism for cell loss in Alzheimer's disease is currently unknown although evidence has implicated an array of contributing factors including oxidative stress and apoptosis. Recently, the potentially critical role of mitochondrial dysfunction in neurodegenerative diseases has become increasingly compelling due to the analysis of the cascade if events preceding neuronal apoptosis. Previous studies have shown that the intracisternal administration of aluminum (A1) to aged white rabbits yields man biochemical and pathological similarities to Alzheimer's disease and further implicated apoptosis. The specific aim of this project was to develop an in vitro model that uses aluminum to trigger the processes of mitochondrial dysfunction in human neuroblastoma (NT2) cells. It is hoped that this model will determine whether mitochondrial damage is a key early event in neurodegeneration. A1 was shown to lead to substantial death of NT2 cells within 24 hours of incubation. Nuclear fragmentation and condensation suggestive of apoptosis was observed as early as 3 hours and increased substantially through 24 hours. Detection of cytochrome c release provided evidence that A1 induced cell death occurred through apoptosis since A1 treated cells exhibited reduced mitochondrial cytochrome c immunoreactivity. Taken together, these results suggest that A1 induces apoptosis in NT2 cells and is subsequently a valid model to test theories of neurodegeneration as well as screen potential therapeutic agents.