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Metabolic enzyme expression in dopaminergic neurons in Parkinson's disease: An in situ hybridization study
Author(s) -
Kingsbury Ann E.,
Cooper Mark,
Schapira Anthony H. V.,
Foster Oliver J. F.
Publication year - 2001
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.1051
Subject(s) - substantia nigra , midbrain , in situ hybridization , biology , dopaminergic , tegmentum , tyrosine hydroxylase , locus coeruleus , brainstem , dopamine , endocrinology , red nucleus , medicine , parkinson's disease , nucleus , neuroscience , gene expression , central nervous system , biochemistry , gene , disease
To clarify the role of neuronal complex 1 activity in idiopathic Parkinson's disease (IPD), expression of mitochondrial mRNA encoding the ND1 subunit of mitochondrial complex I was examined by semiquantitative in situ hybridization histochemistry in melanized neurons of human substantia nigra in IPD cases and control subjects. Expression of mRNA encoding the glycolytic enzyme, aldolase C, was also examined in substantia nigra and other neurons of the midbrain and brain stem. ND1 mRNA expression was strong in melanized substantia nigra neurons but undetectable in nigral glia. Levels of expression in nigral neurons were higher than in neurons of the red nucleus or cranial nerve nuclei, but similar values were obtained in pontine neurons. ND1 mRNA expression was reduced by about 25% in melanized neurons in IPD. There was no relationship between ND1 expression per cell and disease duration or l ‐dopa dosage in the IPD group. No change in ND1 expression was observed in pontine neurons in IPD, and ND1 expression in the locus ceruleus was also unchanged. Melanized nigral neurons expressed lower levels of aldolase C mRNA than other midbrain or brainstem populations in both control and IPD material. These findings suggest that dopamine neurons are more strongly dependent on mitochondrial energy metabolism and oxidative phosphorylation than other brainstem populations. Because mitochondrial complex I activity is significantly reduced in IPD, intrinsically low expression of glycolytic enzymes, together with disease‐related reduction in complex I activity, may be a contributory factor predisposing nigral neurons to injury.