Does monoamine oxidase type B play a role in dopaminergic nerve cell death in Parkinson's disease?
Evidence supports the role of hyperoxidation phenomena in the mechanism of nerve cell death in Parkinson's disease (PD). The oxidative degradation of dopamine, catalyzed by monoamine oxidase type B (MAO-B), produces free radicals and thus could be implicated in the degenerative process. For this reason, we investigated by immunohistochemistry the distribution of MAO-B-containing cells in the midbrain of five patients with PD and five matched control subjects. MAO-B-like immunoreactivity was detected in glial cells, fibers, and neurons. Although most of the MAO-B-positive neurons probably belonged to the raphe dorsalis, we demonstrated by double-labeling immunohistochemistry that some of them were also dopaminergic. MAO-B-positive dopaminergic neurons were present in all dopaminergic groups of the control midbrain. Within the substantia nigra pars compacta, most dopaminergic neurons were located in the dorsal part of the structure. MAO-B-positive dopaminergic neurons were still detected in PD midbrains. Compared with control subjects, the loss of dopaminergic neurons containing MAO-B (-45%) was no higher than that of MAO-B-negative dopaminergic neurons (-59%). The density of MAO-B-positive glial cells varied in the control midbrains: high in the least affected dopaminergic group (the central gray substance) and low in the most affected region (the substantia nigra pars compacta). The density of MAO-B-positive glial cells within dopaminergic cell subgroups in control midbrains were negatively correlated (r = -0.94; p < 0.02) to the estimated neuronal loss in PD. We conclude that the presence of MAO-B in dopamine-containing neurons does not contribute to vulnerability in PD. Moreover, its presence in some glial cells might have a protective effect against oxidative stress induced by dopamine metabolism.
Damier
P
P
INSERM U289, Hôpital de la Salpêtrière, Paris, France.
Kastner
A
A
Agid
Y
Y
Hirsch
E C
EC
D000368:Aged; D001344:Autopsy; D016923:Cell Death; D004298:Dopamine / Q000502:physiology*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008636:Mesencephalon / Q000201:enzymology* / Q000473:pathology*; D008995:Monoamine Oxidase / Q000378:metabolism*; D009457:Neuroglia / Q000201:enzymology / Q000473:pathology*; D009474:Neurons / Q000201:enzymology / Q000473:pathology*; D009928:Organ Specificity; D010300:Parkinson Disease / Q000201:enzymology* / Q000473:pathology*; D012016:Reference Values; D013378:Substantia Nigra / Q000201:enzymology / Q000473:pathology
D007527:Isoenzymes; D008995:Monoamine Oxidase; D004298:Dopamine