title: Different susceptibility to 1-methyl-4-phenylpyridium (MPP(+))-induced nigro-striatal dopaminergic cell loss between C57BL/6 and BALB/c mice is not related to the difference of monoamine oxidase-B (MAO-B).
abstract: Subcutaneous and intraperitoneal administrations of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induce selective dopaminergic (DA-ergic) neuronal death in many animal species. After passing through the blood-brain barrier (BBB), MPTP is converted to 1-methy-4-phenylpiridinium (MPP(+)) by astrocytic monoamine oxidase-B (MAO-B). MPP(+) then induces the dopaminergic neuronal death. In mice, marked strain differences in the susceptibility to MPTP-injection have been reported. To clarify which factor(s) cause the strain differences, MPTP or MPP(+) was intracerebroventricularly (icv) injected into adult C57BL/6 (highly susceptible to MPTP) and BALB/c (resistant to MPTP) mice. The brain tissues including the striatum and substantia nigra pars compacta (SNpc) were examined immunohistochemically using an antibody to tyrosine hydrocyrase (TH). MPP(+)-injected C57BL/6 mice showed a significant decrease in TH-immunopositive areas in the striatum at Day 3 post injection (p<0.01), and TH-positive cells in the SNpc at Days 1 and 3 (p<0.01), respectively, compared to saline-injected control mice. In addition, MPP(+)-injected BALB/c mice showed a significant decrease in TH-positive areas in the striatum at Days 1 and 3, and SNpc TH-positive cells in the SNpc at Day 3, respectively (p<0.05). However, the decrease rates in the BALB/c mice were lower than that in C57BL/6 mice. MPTP-injected C57BL/6 mice, however, showed no lesions in the striatum and SNpc at Days 1 and 7 after icv injection. All the present findings indicate that factors other than MAO-B can influence the strain susceptibility between C57BL/6 and BALB/c mice after the conversion from MPTP to MPP(+).
authors.affiliation: Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-Ku, Tokyo 113-8657, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ito
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Suzuki
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Uchida
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakayama
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D004198:Disease Susceptibility; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D020267:MPTP Poisoning / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008995:Monoamine Oxidase / Q000378:metabolism*; D013045:Species Specificity; D013378:Substantia Nigra / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology
chemical_list: D008995:Monoamine Oxidase; D015655:1-Methyl-4-phenylpyridinium