title: [Behavioral analysis of chronic exposure to diphenylarsinic and associated influence on central nervous systems].
abstract: It has been clinically reported that chronic exposure to diphenylarsinic acid (DPAA) induced prominent cerebellar symptoms in apartment building residents in Kamisu, Japan. The aim of the present study was then to investigate the effect of chronic treatment with DPAA on the central motor impairment in mice. In the present study, we found that chronic in vivo exposure to a high dose of DPAA induced motor impairment in adult mice. This impairment was reversed by withdrawal following chronic DPAA treatment. The [35S]GTPgammaS binding assay showed the down-regulation of the dopamine receptor function in the striatum in adult mice treated with DPAA. We also found that neonatal exposure to a low dose of DPAA induced motor learning impairment in mice. Furthermore, treatment with an extremely low dose of DPAA caused the activation of caspase-3, the increase in glial fibrillary acidic protein-like immunoreactivity (IR) and the reduction in levels of myelin-associated glycoprotein-IR in mouse cerebellum neuron/glia co-cultures. In addition, we found that neonatal exposure to a low dose of DPAA induced anxiogenic behavior in a plus maze in mice. Taken together, these results suggest that chronic treatment with DPAA may induce motor impairment in adult mice. Moreover, neonatal exposure to DPAA leads to the irreversible motor impairment associated with abnormalities in the cerebellum.
authors.affiliation: Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Miyagawa
authors.forename: Minoru
authors.initials: M
authors.lastname: Narita
authors.forename: Mayumi
authors.initials: M
authors.lastname: Miyatake
authors.forename: Koichi
authors.initials: K
authors.lastname: Kato
authors.forename: Kenzo
authors.initials: K
authors.lastname: Yamanaka
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D001008:Anxiety Disorders / Q000139:chemically induced*; D020261:Arsenic Poisoning / Q000209:etiology*; D001152:Arsenicals / Q000009:adverse effects*; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure / Q000009:adverse effects; D005260:Female; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects*; D009069:Movement Disorders / Q000209:etiology*; D009457:Neuroglia / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D011247:Pregnancy; D011596:Psychomotor Disorders / Q000139:chemically induced*; D014874:Water Pollutants, Chemical / Q000009:adverse effects*
chemical_list: D001152:Arsenicals; D014874:Water Pollutants, Chemical; C505409:Casp3 protein, mouse; D053148:Caspase 3; C493087:diphenylarsinic acid