Summary

Degeneration of the substantia nigra with Lewy bodies in remaining neurones is a key pathological marker of Parkinson's disease (PD). A number of observations suggest that processes of oxidative stress are taking place within substantia nigra in PD. Oxidative stress, and the associated finding of reduced activity of complex I of the mitochondrial respiratory chain, might be a primary cause of the pathology of PD. We have tested this hypothesis by examining indices of oxidative stress and mitochondrial enzyme activity in another brain region in which Lewy bodies are known to occur in PD, namely the substantia innominata. We have also examined similar indices in cingulate cortex of brains from patients with senile dementia of the Lewy body type. Tissues from Alzheimer's disease (SDAT) have also been included for comparison. These studies have shown that oxidative stress and altered mitochondrial activity do not necessarily occur in the other regions containing Lewy bodies, although there is evidence for oxidative stress in the same brain regions in SDAT. Oxidative stress and reduced mitochondrial complex I activity appear to be confined to the substantia nigra in PD, and may reflect the peculiar vulnerability of the substantia to such processes.

Introduction

The primary pathology of Parkinson's disease (PD) is the degeneration of the dopamine containing, pigmented neurones of the substantia nigra pars compacta, with Lewy bodies in remaining neurones. Neuronal loss with Lewy bodies is however more widespread involving a range of pigmented catecholamine-containing brain stem nuclei, such as the locus coerulus, as well as non-pigmented, non-catecholamine containing nuclei, such as the substantia innominata.