title: Acute toxicity of MPTP and MPP(+) in the brain of embryo and newborn mice.
abstract: 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) causes damage to dopaminergic neurons in the nigrostriatal system, similar to that seen in Parkinson disease (PD). Recently, a few reports have confirmed neuroblastic apoptosis in the subventricular zone (SVZ) of adult C57BL/6J mice by i.p. injection of MPTP, and concluded that MPTP is also toxic to neuroblasts in the SVZ. While there have been many researches on the neurotoxicity of MPTP in adult mice, there have been only a few in fetal mice. In the present study, we assessed the toxicity of MPTP to embryonic and newborn mice after a single injection into pregnant or newborn mice. MPTP and 1-methyl-4-phenylpyridinium (MPP(+)), a metabolite of MPTP, caused loss of tyrosine hydroxylase (TH)-positive cells or fibers and increased apoptotic cells in embryonic and newborn mice. In addition, MPTP and MPP(+) induced a marked increase of apoptotic cells in the SVZ compared to the nigrostriatal system. The present results may indicate that MPTP and MPP(+) pass through the placenta and blood-brain barrier (BBB) and that a different mechanism may be involved in MPTP- or MPP(+)-induced toxicity in the SVZ and in the nigrostriatal system of embryonic and newborn mice.
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. Takafumi_Sai@nts.toray.co.jp
authors.forename: Takafumi
authors.initials: T
authors.lastname: Sai
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 / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000196:embryology / Q000254:growth & development / Q000473:pathology; D005260:Female; D007150:Immunohistochemistry; D020267:MPTP Poisoning / Q000139:chemically induced / Q000196:embryology* / Q000378:metabolism / Q000473:pathology; D018811:Maternal Exposure / Q000009:adverse effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D038081:Organogenesis / Q000187:drug effects*; D011247:Pregnancy; D023382:Toxicity Tests, Acute
chemical_list: D015655:1-Methyl-4-phenylpyridinium