Suppressive effect of FK-506, a novel immunosuppressant, against MPTP-induced dopamine depletion in the striatum of young C57BL/6 mice.
Systemic injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is known to damage the dopaminergic nigrostriatal system in C57BL/6 mice. We have investigated the effects of immunosuppressants, FK-506 and cyclosporin A (CsA), on MPTP-induced dopamine (DA) depletion in the striatum of young C57BL/6 mice. 10 days after MPTP treatment (25 mg/kg i.p. given daily, 5 days), DA in the striatum was depleted by 80%. However, pretreatment with FK-506, a novel immunosuppressant, significantly protected MPTP-induced DA depletion in the striatum, but FK-506 itself did not affect the DA content. CsA, another immunosuppressant, also protected MPTP-induced DA depletion. From these results can be seen that immunosuppressants seem to inhibit MPTP neurotoxicity toward nigrostriatal dopaminergic neurons of young C57BL/6 mice.
Kitamura
Y
Y
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Itano
Y
Y
Kubo
T
T
Nomura
Y
Y
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism*; D016572:Cyclosporine / Q000494:pharmacology; D004298:Dopamine / Q000172:deficiency*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009638:Norepinephrine / Q000378:metabolism; D010844:Picibanil / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism; D016559:Tacrolimus / Q000494:pharmacology*; D014018:Tissue Distribution
D007166:Immunosuppressive Agents; D012701:Serotonin; D010844:Picibanil; D016572:Cyclosporine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine; D016559:Tacrolimus; D009638:Norepinephrine