title: Reversible aberration of neurogenesis targeting late-stage progenitor cells in the hippocampal dentate gyrus of rat offspring after maternal exposure to acrylamide.
abstract: We have recently shown that maternal exposure to acrylamide (AA) impaired neurogenesis in rat offspring measured by the increase in interneurons producing reelin, a molecule regulating migration and correct positioning of developing neurons, in the hippocampal dentate gyrus. To clarify the cellular target of AA on hippocampal neurogenesis and its reversibility after maternal exposure, pregnant Sprague-Dawley rats were given drinking water containing AA at 0, 4, 20, 100 ppm on day 10 of pregnancy through day 21 after delivery on weaning. Male offspring were examined immunohistochemically on postnatal day (PND) 21 and PND 77. For comparison, male pups of direct AA-injection control during lactation (50 mg/kg body weight, intraperitoneally, 3 times/week) were also examined. On PND 21, maternal AA-exposure decreased progenitor cell proliferation in the subgranular zone (SGZ) from 20 ppm accompanied with increased density of reelin-producing interneurons and NeuN-expressing mature neurons within the hilus at 100 ppm, similar to the direct AA-injection control. In the SGZ examined at 100 ppm, cellular populations immunoexpressing doublecortin or dihydropyrimidinase-like 3, suggesting postmitotic immature granule cells, were decreased. On PND 77, the SGZ cell proliferation and reelin-producing interneuron density recovered, while the hilar mature neurons sustained to increase from 20 ppm, similar to the direct AA-injection control. Thus, developmental exposure to AA reversibly affects hippocampal neurogenesis targeting the proliferation of type-3 progenitor cells resulting in a decrease in immature granule cells in rats. A sustained increase in hilar mature neurons could be the signature of the developmental effect of AA.
authors.affiliation: Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509, Japan.
authors.forename: Bunichiro
authors.initials: B
authors.lastname: Ogawa
authors.forename: Liyun
authors.initials: L
authors.lastname: Wang
authors.forename: Takumi
authors.initials: T
authors.lastname: Ohishi
authors.forename: Eriko
authors.initials: E
authors.lastname: Taniai
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Akane
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Suzuki
authors.forename: Kunitoshi
authors.initials: K
authors.lastname: Mitsumori
authors.forename: Makoto
authors.initials: M
authors.lastname: Shibutani
mesh_terms: D020106:Acrylamide / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D018891:Dentate Gyrus / Q000187:drug effects* / Q000254:growth & development; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D060766:Drinking Water; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008297:Male; D018811:Maternal Exposure; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D060766:Drinking Water; D016326:Extracellular Matrix Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D000091042:Reelin Protein; C000717129:Reln protein, rat; D020106:Acrylamide; D012697:Serine Endopeptidases