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