| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1992: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1991: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Research Abstract |
For synthesis of catecholamines, two synthetic enzymes are at least needed. One is tyrosine hydroxylase (TH), which converts tyrosine to L-DOPA, and another is aromatic L-amino acid decarboxylase (AADC), which converts L-DOPA to dopamine. It has been demonstrated that there is a group of neurons containing AADC but lacks TH in the brain, but its functional roles is still unclear. In the present study, we investigated the possibility that these central AADC(+)/TH(-) neurons have the ability to "amine precursor uptake and decarboxylation (APUD). I. Distribution of APUD cells in the rat central nervous system Male Wistar rats were sacrificed 60 min after loading of L-DOPA (20 mg/kg, i.p.). They were processed for double labeling immunocytochemistry using mouse monoclonal anti-dopamine serum and rabbit anti-AADC serum. All the AADC-immunoreactive cells in the brain showed dopamine-immunoreactivity. This suggest that non-aminergic AADC neurons have ability to convert amine precursor to amines (APUD-activity). II. Projection of cenral APUD cells Gold labeled choleratoxin-B, a retrograde neuronal tracer, were injected into the hippocampus, amygdala and septum, and into various region of the hypothalamus. These rats were processed for AADC or TH immunocytochemistry. These investigations have revealed supramammillary nonaminergic AADC neurons project to the hippocampus, but other non-aminergic AADC neurons innervate only in the hypothalamus. only inside the hypothalamus. III. Uptake of [3H]DOPA After 60 min of [3H]DOPA injection, we performed in vivo autoradiography. High density of isotope-labeling was detected in the caudate-putamen, nucleus accumbens, and tuberculum olfactorium. Hypothalamus showed weak but distinct labeling. This suggest that hypothalamus, a region rich in non-aminergic AADC neurons and fibers, have lower ability for uptaking DOPA than that of caudate-putamen, in which abundant nigrostriatal dopaminergic endings are found.
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