Late Effect of Developmental Exposure to 3,3'-Iminodipropionitrile on Neurogenesis in the Hippocampal Dentate Gyrus of Mice.
The effects of developmental exposure to 3,3'-iminodipropionitrile (IDPN), a neurotoxicant that causes proximal axonopathy, on mouse hippocampal neurogenesis was examined. Pregnant mice were exposed to IDPN at 0, 600, or 1200 ppm in their drinking water from gestational day 6 to postnatal day (PND) 21. On PND 21, male offspring showed increased postmitotic neuron-specific NeuN-immunoreactive(+)granule cell numbers in the dentate subgranular zone (SGZ) and granule cell layer (GCL) and decreased glutamate receptor gene Grin2d levels in the dentate gyrus at 1200 ppm. On PND 77, decreased numbers were observed for TBR2+progenitor cells in the SGZ at ≥600 ppm and GFAP+stem cells, DCX+progenitor cells and immature granule cells, NeuN+immature and mature granule cells, PCNA+proliferating cells in the SGZ and/or GCL, and immunoreactive cells for ARC or FOS, immediate-early gene products related to neuronal and synaptic plasticity, in the GCL at 1200 ppm. Additionally, at 1200 ppm of IDPN, downregulation of Kit, the gene encoding the stem cell factor (SCF) receptor, and upregulation of Kitl, encoding SCF, were observed in the dentate gyrus. Therefore, maternal IDPN exposure in mice affects neurogenesis involving glutamatergic signals at the end of developmental exposure, with late effects suppressing SGZ cell proliferation, reducing the broad range of granule cell lineage population, which may be responsible for SCF receptor downregulation. The upregulated SCF was likely a feedback response to the decreased receptor level. These results suggest that reduced SCF signaling may cause suppressed neuronal and synaptic plasticity.
Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo, 183-8509, Japan.
Yasuko
Y
Hasegawa-Baba
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.
Takeshi
T
Tanaka
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.
Yousuke
Y
Watanabe
Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo, 183-8509, Japan.
Liyun
L
Wang
Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo, 183-8509, Japan.
Megu
M
Itahashi
Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo, 183-8509, Japan.
Toshinori
T
Yoshida
Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo, 183-8509, Japan. mshibuta@cc.tuat.ac.jp.
Makoto
http://orcid.org/0000-0003-3417-9697
M
Shibutani
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003598:Cytoskeletal Proteins / Q000378:metabolism; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects / Q000196:embryology / Q000254:growth & development; D000089662:Doublecortin Protein; D004622:Embryo, Mammalian; D000071438:Fatty Acid-Binding Protein 7 / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D009336:Necrosis / Q000139:chemically induced; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects*; D009570:Nitriles / Q000494:pharmacology*; D016761:Oncogene Proteins v-fos / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism
D003598:Cytoskeletal Proteins; C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein; C491198:Eomes protein, mouse; C086936:Fabp7 protein, mouse; D000071438:Fatty Acid-Binding Protein 7; D009419:Nerve Tissue Proteins; D009570:Nitriles; D016761:Oncogene Proteins v-fos; D018809:Proliferating Cell Nuclear Antigen; D020825:T-Box Domain Proteins; C092069:activity regulated cytoskeletal-associated protein; C008110:3,3'-iminodipropionitrile
3,3′-Iminodipropionitrile (IDPN); Hippocampal dentate gyrus; Late effect; Mouse; Neurogenesis