Parkinson's disease is associated with oxidative damage to cytoplasmic DNAand RNA in substantia nigra neurons

Citation
J. Zhang et al., Parkinson's disease is associated with oxidative damage to cytoplasmic DNAand RNA in substantia nigra neurons, AM J PATH, 154(5), 1999, pp. 1423-1429
Citations number
40
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research Diagnosis & Treatment
Journal title
AMERICAN JOURNAL OF PATHOLOGY
ISSN journal
0002-9440 → ACNP
Volume
154
Issue
5
Year of publication
1999
Pages
1423 - 1429
Database
ISI
SICI code
0002-9440(199905)154:5<1423:PDIAWO>2.0.ZU;2-#
Abstract
Oxidative damage, including modification of nucleic acids, may contribute t o dopaminergic neurodegeneration in the substantia nigra (SN) of patients w ith Parkinson's disease (PD). To investigate the extent and distribution of nucleic acid oxidative damage in these vulnerable dopaminergic neurons, we immunohistochemically characterized a common product of nucleic acid oxida tion, 8-hydroxyguanosine (8OHG). In PD patients, cytoplasmic 8OHG immunorea ctivity was intense in neurons of the SN, and present to a lesser extent in neurons of the nucleus raphe dorsalis and oculomotor nucleus, and occasion ally in glia. The proportion of 8OHG immunoreactive SN neurons was signific antly greater in PD patients compared to age-matched controls. Midbrain sec tions from patients with multiple system atrophy-Parkinsonian type (MSA-P) and dementia with Lewy bodies (DLB) also were examined. These showed increa sed cytoplasmic 8OHG immunoreactivity in SN neurons in both MSA-P and DLB c ompared to controls; however, the proportion of positive neurons was signif icantly less than in PD patients. The regional distribution of 8OHG immunor eactive neurons within the SN corresponded to the distribution of neurodege neration for these three diseases. Nuclear 8OHG immunoreactivity was not ob served in any individual. The type of cytoplasmic nucleic acid responsible for 8OHG immunoreactivity was analyzed by preincubating midbrain sections f rom PD patients with RNase, DNase, or both enzymes. 8OHG immunoreactivity w as substantially diminished by either RNase or DNase, and completely ablate d by both enzymes. These results suggest that oxidative damage to cytoplasm ic nucleic acid is selectively increased in midbrain, especially the SN, of PD patients and much less so in MSA-P and DLB patients. Moreover, oxidativ e damage to nucleic acid is largely restricted to cytoplasm with both RNA a nd mitochondrial DNA as targets.