Gabaergic transmission and tyrosine hydroxylase expression in the nigral dopaminergic neurons: an in vivo study using a reversible ischemia model of rats.
The authors conducted an in vivo study, using a rat striatal ischemic model, of the effect of GABAergic transmission upon the dopamine synthesizing enzyme tyrosine hydroxylase in the neurons of the substantia nigra pars compacta. Two hours transient middle cerebral artery occlusion produced massive striatal ischemic damage resulting in a marked decrease of GABAergic projection to the ipsilateral substantia nigra. Histological examinations were conducted in rats killed at three, seven, 15, 30 and 94 days after ischemia. The immunoreactivity for tyrosine hydroxylase in the ipsilateral pars compacta was unaltered up to three days after the ischemic insult, but it was markedly decreased at seven days post-ischemia. At this stage, the number of neurons positive for tyrosine hydroxylase was significantly decreased in the ipsilateral pars compacta, whereas there was no significant reduction in the number of pars compacta neurons containing Nissl substance. By 30 days post-ischemia, the tyrosine hydroxylase-positive cell number in the ipsilateral pars compacta appeared to be equivalent to that of the contralateral side. It was also noted that continuous intraventricular administration of a GABAA receptor agonist muscimol, initiated from 24 h post-ischemia, effectively prevented the transient reduction of immunoreactivity for tyrosine hydroxylase in the ipsilateral pars compacta at seven and 15 days after ischemic insult. The present study revealed that the striatal ischemic lesion induced a transient down-regulation of tyrosine hydroxylase synthesis in the pars compacta neurons, which could be prevented by administration of GABA agonist, suggesting that GABAergic transmission greatly affects dopamine metabolism in these cells.
Yamada
K
K
Department of Neurosurgery, Kumamoto University Medical School, Japan.
Goto
S
S
Yoshikawa
M
M
Ushio
Y
Y
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D002452:Cell Count; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine