title: Diphenylarsinic acid increased the synthesis and release of neuroactive and vasoactive peptides in rat cerebellar astrocytes.
abstract: An incident of poisoning occurred in Japan in 2003 when high-level contamination with arsenic, mainly diphenylarsinic acid (DPAA), was found in well water. People using this water particularly experienced cerebellar symptoms. In the present study, we investigated the adverse effects of DPAA on the cerebellum in vitro and in vivo to understand the biological mechanisms that cause cerebellar symptoms. Comprehensive gene expression analyses in primary cultured ratcerebellar cells exposed to 10 μM DPAA for 24 hours indicated significant alterations in the mRNA expression of genes encoding antioxidative stress proteins (heme oxigenase 1 and heat shock protein72) and neuroactive and vasoactive peptides (neuropeptide Y, adrenomedullin, monocyte chemoattractant protein 1, and fibroblast growth factor 2). Further analyses of proteins revealed that cultured cerebellar astrocytes expressed these antioxidative stress proteins and peptides in response to exposure to DPAA. In addition, these adverseeffects were also observed in the cerebellum exposed in vivo to DPAA (100 mg/L) for 21 days. These results suggested that cerebellarastrocytes irregularly secrete neuroactive and vasoactive peptidesagainst DPAA-induced oxidative stress, which leads to abnormal neural functions and disrupted cerebellar autoregulation dynamics and results in the onset of cerebellar symptoms.
authors.affiliation: Department of Chemistry and Biological Science, Aoyama Gakuin University, Chuo-ku, Sagamihara-shi, Kanagawa, Japan. taka-u@yayoi.club.ne.jp
authors.forename: Takayuki
authors.initials: T
authors.lastname: Negishi
authors.forename: Masaki
authors.initials: M
authors.lastname: Takahashi
authors.forename: Yuki
authors.initials: Y
authors.lastname: Matsunaga
authors.forename: Seishiro
authors.initials: S
authors.lastname: Hirano
authors.forename: Tomoko
authors.initials: T
authors.lastname: Tashiro
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001152:Arsenicals / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D007150:Immunohistochemistry; D008297:Male; D046228:Microarray Analysis; D009043:Motor Activity / Q000187:drug effects; D009479:Neuropeptides / Q000096:biosynthesis*; D010455:Peptides / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000975:Antioxidants; D001152:Arsenicals; D009479:Neuropeptides; D010455:Peptides; D012333:RNA, Messenger; C493087:diphenylarsinic acid