Significant reduction of 125 I-meta-iodobenzylguanidine accumulation directly caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydroxypyridine, a toxic agent for inducing experimental Parkinson's disease.
A significant reduction of cardiac 123I-meta-iodobenzylguanidine (MIBG) accumulation has been reported in patients with idiopathic Parkinson's disease. However, it is unclear whether this reduction in cardiac sympathetic nerve is caused primarily or secondarily to the degeneration of sympathetic nerve centres which occurs in Parkinson's disease. Therefore, we examined neuronal 125I-MIBG accumulation in mice hearts of an experimental Parkinson's disease model and in sympathetic cells without any neuronal innervation. Cardiac accumulation of 125I-MIBG was determined 4h after intravenous injection of 125I-MIBG in mice pretreated with 1-methyl-4-phenyl-1,2,3,6-tetrahydroxypyridine (MPTP), an inducer of Parkinson's disease. In an in vitro study, uptake of 125I-MIBG was determined in a cultured pheochromocytoma cell line (PC-12), which was pretreated with MPTP. MPTP reduced MIBG accumulation mainly in its neuronal component of mice hearts, suggesting that MPTP impairs cardiac sympathetic nerves to uptake MIBG. Application of MPTP also caused near-complete blockade of 125I-MIBG accumulation in PC-12 cells. In the experimental PD models, it was shown that neuronal accumulation of MIBG was impaired by the direct action of MPTP to the sympathetic cells. These findings support the idea that cardiac sympathetic nerves are primarily impaired in Parkinson's disease despite the presence or absence of systemic autonomic failure.
Takatsu
H
H
First Department of Internal Medicine, Gifu Municipal Hospital, Japan. htakatsu-gif@u.ac.jp
Wada
H
H
Maekawa
N
N
Takemura
M
M
Saito
K
K
Fujiwara
H
H
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D019797:3-Iodobenzylguanidine / Q000493:pharmacokinetics*; D000818:Animals; D002478:Cells, Cultured; D003891:Desipramine / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology*; D006321:Heart / Q000000981:diagnostic imaging; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism; D009474:Neurons / Q000000981:diagnostic imaging / Q000378:metabolism*; D016716:PC12 Cells; D020734:Parkinsonian Disorders / Q000139:chemically induced*; D011877:Radionuclide Imaging; D051381:Rats
D015259:Dopamine Agents; D007457:Iodine Radioisotopes; D019797:3-Iodobenzylguanidine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D003891:Desipramine