title: Age-related dopamine deficiency in the mesostriatal dopamine system of zitter mutant rats: regional fiber vulnerability in the striatum and the olfactory tubercle.
abstract: Oxidant stress has been implicated in the pathogenesis of Parkinson's disease. To test the oxidant stress hypothesis of dopaminergic degeneration, age-related changes in the mesostriatal dopamine neuron system were compared between zitter mutant rats which have abnormal metabolism of oxygen species in the brain and Sprague-Dawley rat as a control using the neurochemistry and immunohistochemistry. Dopamine content in the caudate-putamen, nucleus accumbens and olfactory tubercle of zitter rats decreased significantly with age, and was lower than that found in corresponding age-matched controls. In the zitter rats, the reduction of dopamine was more prominent in the caudate-putamen than in the nucleus accumbens and olfactory tubercle. A characteristic decline of tyrosine hydroxylase-immunoreactive fibers in the caudate-putamen of the zitter rat was also observed. In the dorsolateral caudate-putamen, reduction of tyrosine hydroxylase-immunoreactive fibers was observed in the matrix-like area, whereas in the ventromedial caudate-putamen the reduction occurred in the patch-like areas. Degeneration of tyrosine hydroxylase-immunoreactive fibers which was characterized by swollen varicosities and clustered fibers was observed in the caudate-putamen and nucleus accumbens and preceded loss of normal tyrosine hydroxylase-immunoreactive fibers in the caudate-putamen. Thus, the depletion of dopamine in the terminal areas is related to axonal degeneration. However, there was no degenerative tyrosine hydroxylase-immunoreactive fibers in the olfactory tubercle at any examined age, but reductions of tyrosine hydroxylase-immunoreactive fibers and dopamine contents were noted in the olfactory tubercle after four months-of-age. Since the zitter rats have an abnormal oxygen metabolism, the degeneration of tyrosine hydroxylase-immunoreactive fibers could result from an accumulation of superoxide species. The present results provide support for the oxidant stress hypothesis of dopaminergic neuronal degeneration and further indicate the region-specific vulnerability of the nigrostriatal dopamine system.
authors.affiliation: Department of Histology and Neurobiology, Dokkyo University School of Medicine, Mibu, Tochigi, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Ueda
authors.forename: M
authors.initials: M
authors.lastname: Aikawa
authors.forename: A
authors.initials: A
authors.lastname: Ishizuya-Oka
authors.forename: S
authors.initials: S
authors.lastname: Yamaoka
authors.forename: N
authors.initials: N
authors.lastname: Koibuchi
authors.forename: K
authors.initials: K
authors.lastname: Yoshimoto
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis / Q000378:metabolism; D000375:Aging / Q000502:physiology*; D000818:Animals; D000906:Antibodies; D004195:Disease Models, Animal; D004298:Dopamine / Q000032:analysis / Q000172:deficiency*; D005609:Free Radicals / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000032:analysis / Q000378:metabolism; D017072:Neostriatum / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D009412:Nerve Fibers / Q000737:chemistry / Q000201:enzymology; D009638:Norepinephrine / Q000032:analysis / Q000378:metabolism; D009714:Nucleus Accumbens / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D009833:Olfactory Pathways / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D010302:Parkinson Disease, Secondary / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000032:analysis / Q000378:metabolism; D013378:Substantia Nigra / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis / Q000276:immunology
chemical_list: D000906:Antibodies; D005609:Free Radicals; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D009638:Norepinephrine