Age-related dopamine deficiency in the mesostriatal dopamine system of zitter mutant rats: Regional fiber vulnerability in the striatum and the olfactory tubercle

Citation
S. Ueda et al., Age-related dopamine deficiency in the mesostriatal dopamine system of zitter mutant rats: Regional fiber vulnerability in the striatum and the olfactory tubercle, NEUROSCIENC, 95(2), 2000, pp. 389-398
Citations number
47
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
NEUROSCIENCE
ISSN journal
0306-4522 → ACNP
Volume
95
Issue
2
Year of publication
2000
Pages
389 - 398
Database
ISI
SICI code
0306-4522(2000)95:2<389:ADDITM>2.0.ZU;2-Q
Abstract
Oxidant stress has been implicated in the pathogenesis of Parkinson's disea se. To test the oxidant stress hypothesis of dopaminergic degeneration, age -related changes in the mesostriatal dopamine neuron system were compared b etween titter mutant rats which have abnormal metabolism of oxygen species in the brain and Sprague-Dawley rat as a control using the neurochemistry a nd immunohistochemistry. Dopamine content in the caudate-putamen, nucleus a ccumbens and olfactory tubercle of titter rats decreased significantly with age, and was lower than that found in corresponding age-matched controls. in the titter rats, the reduction of dopamine was more prominent in the cau date-putamen than in the nucleus accumbens and olfactory tubercle. A charac teristic decline of tyrosine hydroxylase immunoreactive fibers in the cauda te-putamen of the titter rat was also observed. In the dorsolateral caudate -putamen, reduction of tyrosine hydroxylase-immunoreactive fibers was obser ved in the matrix-like area, whereas in the ventromedial caudate-putamen th e reduction occurred in the patch-like areas. Degeneration of tyrosine hydr oxylase-immunoreactive fibers which was characterized by swollen varicositi es and clustered fibers was observed in the caudate-putamen and nucleus acc umbens and preceded loss of normal tyrosine hydroxylase immunoreactive fibe rs 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 an y examined age, but reductions of tyrosine hydroxylase-immunoreactive fiber s and dopamine contents were noted in the olfactory tubercle after four mon ths-of-age. Since the zitter rats have an abnormal oxygen metabolism, the degeneration of tyrosine hydroxylase-immunoreactive fibers could result from an accumula tion of superoxide species. The present results provide support for the oxi dant stress hypothesis of dopaminergic neuronal degeneration and further in dicate the region-specific vulnerability of the nigrostriatal dopamine syst em. (C) 1999 IBRO. Published by Elsevier Science Ltd.