title: Maternal exposure to 3,3'-iminodipropionitrile targets late-stage differentiation of hippocampal granule cell lineages to affect brain-derived neurotrophic factor signaling and interneuron subpopulations in rat offspring.
abstract: 3,3'-Iminodipropionitrile (IDPN) causes neurofilament (NF)-filled swellings in the proximal segments of many large-caliber myelinated axons. This study investigated the effect of maternal exposure to IDPN on hippocampal neurogenesis in rat offspring using pregnant rats supplemented with 0 (controls), 67 or 200 ppm IDPN in drinking water from gestational day 6 to day 21 after delivery. On postnatal day (PND) 21, female offspring subjected to analysis had decreased parvalbumin(+), reelin(+) and phospho-TrkB(+) interneurons in the dentate hilus at 200 ppm and increased granule cell populations expressing immediate-early gene products, Arc or c-Fos, at ≥  67 ppm. mRNA expression in the dentate gyrus examined at 200 ppm decreased with brain-derived neurotrophic factor (Bdnf) and very low density lipoprotein receptor. Immunoreactivity for phosphorylated NF heavy polypeptide decreased in the molecular layer of the dentate gyrus and the stratum radiatum of the cornu ammonis (CA) 3, portions showing axonal projections from mossy cells and pyramidal neurons, at 200 ppm on PND 21, whereas immunoreactivity for synaptophysin was unchanged in the dentate gyrus. Observed changes all disappeared on PND 77. There were no fluctuations in the numbers of apoptotic cells, proliferating cells and subpopulations of granule cell lineage in the subgranular zone on PND 21 and PND 77. Thus, maternal IDPN exposure may reversibly affect late-stage differentiation of granule cell lineages involving neuronal plasticity as evident by immediate-early gene responses to cause BDNF downregulation resulting in a reduction in parvalbumin(+) or reelin(+) interneurons and suppression of axonal plasticity in the mossy cells and CA3 pyramidal neurons.
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: Megu
authors.initials: M
authors.lastname: Itahashi
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.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: Takeshi
authors.initials: T
authors.lastname: Tanaka
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: Sayaka
authors.initials: S
authors.lastname: Mizukami
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: Yoh
authors.initials: Y
authors.lastname: Kikuchihara
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: Toshinori
authors.initials: T
authors.lastname: Yoshida
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: Makoto
authors.initials: M
authors.lastname: Shibutani
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology*; D056654:CA3 Region, Hippocampal / Q000166:cytology / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D019070:Cell Lineage / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects; D005260:Female; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D007395:Interneurons / Q000187:drug effects*; D008079:Lipoproteins, VLDL / Q000187:drug effects; D016900:Neurofilament Proteins / Q000378:metabolism; D009570:Nitriles / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D000091042:Reelin Protein; D015398:Signal Transduction / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D008079:Lipoproteins, VLDL; D016900:Neurofilament Proteins; D009570:Nitriles; D000091042:Reelin Protein; C000717129:Reln protein, rat; C008110:3,3'-iminodipropionitrile; D005680:gamma-Aminobutyric Acid
keywords: 3,3’-iminodipropionitrile; brain-derived neurotrophic factor; hippocampal dentate gyrus; neuritogenesis; phosphorylated neurofilament, heavy polypeptide; γ-aminobutyric acid-ergic interneuron