title: Exposure to MnCl2 · 4H2O during development induces activation of microglial and perivascular macrophage populations in the hippocampal dentate gyrus of rats.
abstract: Developmental exposure to Mn caused Mn accumulation in the brain tissue and transient disruption of granule cell neurogenesis, targeting the late stage differentiation of progenitor cells in the subgranular zone of the hippocampal dentate gyrus of rats. Because neurogenesis is influenced by proinflammatory responses, this study was performed to determine whether Mn exposure causes microglial activation in the dentate hilus, a region anatomically close to the subgranular zone of the dentate gyrus. Pregnant rats were treated with dietary MnCl2 · 4H2O at 32, 160 or 800 ppm from gestational day 10 to day 21 after delivery. An immunohistochemical analysis revealed increases in Iba1(+) microglia in the hilus on postnatal day 21 following exposure to MnCl2 · 4H2O in a dose-unrelated manner at 32 and at 800 ppm and an increase in CD163(+) macrophage at 800 ppm in the hilus. Real-time reverse transcription-polymerase chain reaction analysis revealed increases in the mRNA levels of Il1α, Il6, Nos2 and Tnf after 800 ppm MnCl2 · 4H2O. These results suggest that activation of microglia and perivascular macrophages occurs in the hilus after developmental exposure to MnCl2 · 4H2O at 800 ppm, and probably involves the disruption of neurogenesis through the accumulation of Mn in the brain tissue.
authors.affiliation: Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo, 183-8509, Japan; Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu, 501-1193, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Abe
authors.forename: Takumi
authors.initials: T
authors.lastname: Ohishi
authors.forename: Fumiyuki
authors.initials: F
authors.lastname: Nakane
authors.forename: Ayako
authors.initials: A
authors.lastname: Shiraki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tanaka
authors.forename: Toshinori
authors.initials: T
authors.lastname: Yoshida
authors.forename: Makoto
authors.initials: M
authors.lastname: Shibutani
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002712:Chlorides / Q000633:toxicity*; D018891:Dentate Gyrus / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D017895:Manganese Compounds; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells
chemical_list: D002712:Chlorides; D053583:Interleukin-1beta; D015850:Interleukin-6; D017895:Manganese Compounds; D012333:RNA, Messenger; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C025340:manganese chloride
keywords: developmental neurotoxicity; hippocampal dentate gyrus; manganese; microglia; neurogenesis; proinflammatory cytokine