title: Increased expression of aquaporin-4 with methylmercury exposure in the brain of the common marmoset.
abstract: The relationship between methylmercury (MeHg) exposure and aquaporin (AQP) expression in the brain is currently unknown. To investigate this, we used a common marmoset model of acute MeHg exposure to examine AQP1, AQP4 and AQP11 gene expression. MeHg (1.5 mg Hg/kg/day p.o.) was given to three marmosets for 14 days, followed by 14 days without. All treated marmosets showed slight akinesia before sacrifice. In the frontal lobe, occipital lobe and cerebellum, total mercury concentrations following MeHg administration were 26.7, 31.4, and 22.6 µg/g, respectively. Slight apoptosis was observed in the occipital lobe. Immunohistochemistry showed increased expression of glial fibrillary acidic protein, its mRNA and Iba1 with MeHg, indicating that neuronal injury activated astrocytes and microglia. There was no significant difference between control and MeHg-administered groups in AQP1 protein or AQP11 mRNA in the frontal lobe, occipital lobe or cerebellum. The ratio of AQP4 mRNA expression in MeHg-administered marmosets to the mean AQR4 expression in the controls (n = 3) were 1.3, 1.5 and 1.2, 1.7, 1.9 and 1.5, and 1.5, 1.6 and 1.2 for the frontal lobe, occipital lobe and cerebellum, respectively. Western blotting showed significantly increased AQP4 protein in the occipital lobe and cerebellum with MeHg administration, but no obvious up-regulation in the frontal lobe. Immunofluorescence analysis with double staining revealed low AQP4 expression in the cell body of reactive astrocytes in the MeHg-administered group. These results indicate that AQP4 expression might be stimulated by MeHg exposure in astrocytes in the occipital lobe and cerebellum, suggesting a role for AQP4 in MeHg neurotoxicity via astrocyte dysfunction.
authors.affiliation: Department of Basic Medical Sciences, National Institute for Minamata Disease, Kumamoto, Japan. yamamoto@nimd.go.jp
authors.forename: Megumi
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Motohiro
authors.initials: M
authors.lastname: Takeya
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ikeshima-Kataoka
authors.forename: Masato
authors.initials: M
authors.lastname: Yasui
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Kawasaki
authors.forename: Mitsuya
authors.initials: M
authors.lastname: Shiraishi
authors.forename: Eiji
authors.initials: E
authors.lastname: Majima
authors.forename: Seiji
authors.initials: S
authors.lastname: Shiraishi
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Uezono
authors.forename: Masanori
authors.initials: M
authors.lastname: Sasaki
authors.forename: Komyo
authors.initials: K
authors.lastname: Eto
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051401:Aquaporin 4 / Q000235:genetics / Q000378:metabolism*; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology; D002144:Callithrix; D002531:Cerebellum / Q000187:drug effects* / Q000473:pathology; D005260:Female; D005625:Frontal Lobe / Q000187:drug effects* / Q000473:pathology; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D008767:Methylmercury Compounds / Q000633:toxicity*; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D009778:Occipital Lobe / Q000187:drug effects* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D051401:Aquaporin 4; D005904:Glial Fibrillary Acidic Protein; D008767:Methylmercury Compounds; D012333:RNA, Messenger; C004925:methylmercuric chloride