Depletion of
reduced glutathione occurs in the substantia nigra in
Parkinson's disease and in incidental
Lewy body disease (presymptomatic
Parkinson's disease) which may implicate oxidative stress in the neurodegenerative process. In this study
mercury orange fluorescent staining and immunostaining with an antibody to
reduced glutathione have been used to determine the distribution of
reduced glutathione in the substantia nigra in
Parkinson's disease compared with normal individuals.
Mercury orange staining showed moderate background levels of fluorescence in the neuropil in both control and
Parkinson's disease substantia nigra and localised
reduced glutathione to the somata of melanized nigral neurons and glial elements of the neuropil. Neuronal nuclei revealed a relative lack of fluorescence after
mercury orange staining. There was a significant depletion of
reduced glutathione in surviving neurons in
Parkinson's disease compared to nerve cell populations in control tissue.
Mercury orange fluorescence indicated a high concentration of
reduced glutathione in a subpopulation of non-neuronal cells, most likely astrocytes or microglia. Immunohistochemical examination of nigral tissue from the same
Parkinson's disease and control patients with an antibody to
glutathione showed staining in neuronal perikarya and axonodendritic processes of melanized nigral neurons which was generally most intense in control neurons. Moderately intense staining of the background neuropil, most prominent in control nigras, and staining of capillary walls was also detected. Intense staining was seen in cells with the morphological features of glial cells in both control and PD nigra. These data show a significant presence of
reduced glutathione in the cell bodies and axons of nigral neurons. They are in agreement with biochemical studies showing depletion of
reduced glutathione in substantia nigra in
Parkinson's disease, and indicate a significant loss of neuronal
reduced glutathione in surviving nigral neurons in
Parkinson's disease.