title: Maternal exposure to hexachlorophene targets intermediate-stage progenitor cells in the hippocampal neurogenesis involving myelin vacuolation of cholinergic and glutamatergic inputs in mice.
abstract: Hexachlorophene (HCP) has been shown to induce myelin vacuolation due to intramyelinic edema of the nerve fibers in animal neural tissue. We investigated the maternal exposure effect of HCP on hippocampal neurogenesis in the offspring of pregnant mice supplemented with 0 (control), 33 or 100 ppm HCP in diet from gestational day 6 to day 21 after delivery. On postnatal day (PND) 21, offspring as examined in males exhibited decreased granule cell lineage populations expressing paired box 6, sex-determining region Y-box 2 and eomesodermin in the hippocampal subgranular zone (SGZ) accompanied by myelin vacuolation involving white matter tracts of the hippocampal fimbria at ≥ 33 ppm. However, SGZ cellular populations expressing brain lipid binding protein and doublecortin were unchanged at any dose. Transcript expression of cholinergic receptor genes, Chrna4 and Chrnb2, and glutamate receptor genes, Grm1 and Grin2d, examined at 100 ppm, decreased in the dentate gyrus. HCP exposure did not alter the number of proliferating or apoptotic cells in the SGZ, or reelin- or calcium-binding protein-expressing γ-aminobutyric acid (GABA)ergic interneurons in the dentate hilus, on PND 21 and PND 77. All neurogenesis-related changes observed in HCP-exposed offspring on PND 21 disappeared on PND 77, suggesting that maternal HCP exposure at ≥ 33 ppm reversibly decreased type 2 intermediate-stage progenitor cells in the hippocampal neurogenesis. Myelin vacuolation might be responsible for changes in neurogenesis possibly by reducing nerve conduction velocity of cholinergic inputs from the septal-hippocampal pathway to granule cell lineages and/or GABAergic interneurons, and of glutamatergic inputs to granule cell lineages.
authors.affiliation: Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, Fuchu-shi, Tokyo, Japan.
authors.forename: Mizuho
authors.initials: M
authors.lastname: Kato
authors.affiliation: Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, Fuchu-shi, Tokyo, Japan.|Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, Gifu-shi, Gifu, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Abe
authors.affiliation: Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, Fuchu-shi, Tokyo, Japan.|Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, Gifu-shi, Gifu, Japan.
authors.forename: Megu
authors.initials: M
authors.lastname: Itahashi
authors.affiliation: Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, Fuchu-shi, Tokyo, Japan.
authors.forename: Yoh
authors.initials: Y
authors.lastname: Kikuchihara
authors.affiliation: Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, Fuchu-shi, Tokyo, Japan.|Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, Gifu-shi, Gifu, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kimura
authors.affiliation: Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, Fuchu-shi, Tokyo, Japan.|Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, Gifu-shi, Gifu, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Mizukami
authors.affiliation: Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, Fuchu-shi, Tokyo, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, Fuchu-shi, Tokyo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Shibutani
mesh_terms: D000818:Animals; D018678:Cholinergic Agents / Q000378:metabolism; D018683:Excitatory Amino Acid Agents / Q000378:metabolism; D005260:Female; D006582:Hexachlorophene / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D051379:Mice; D009186:Myelin Sheath / Q000187:drug effects*; D055495:Neurogenesis / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D000091042:Reelin Protein; D013234:Stem Cells / Q000187:drug effects*
chemical_list: D018678:Cholinergic Agents; D018683:Excitatory Amino Acid Agents; D000091042:Reelin Protein; C000717128:Reln protein, mouse; D006582:Hexachlorophene
keywords: cholinergic neuron; cholinergic receptor; glutamatergic receptor; hexachlorophene; hippocampal neurogenesis; myelin vacuolation