Makoto Shibutani


Affiliation: Tokyo University of Agriculture and Technology
Country: Japan


  1. Nakajima K, Tanaka T, Masubuchi Y, Ito Y, Kikuchi S, Woo G, et al. Developmental Exposure of Mice to T-2 Toxin Increases Astrocytes and Hippocampal Neural Stem Cells Expressing Metallothionein. Neurotox Res. 2019;35:668-683 pubmed publisher
    ..The increase of MT-I/II+ cells in all brain regions disappeared or was suppressed below the control level on PND 77, suggesting a recovery from the T-2 toxin-induced oxidative stress. ..
  2. Nakajima K, Masubuchi Y, Ito Y, Inohana M, Takino M, Saegusa Y, et al. Developmental exposure of citreoviridin transiently affects hippocampal neurogenesis targeting multiple regulatory functions in mice. Food Chem Toxicol. 2018;120:590-602 pubmed publisher
    ..The no-observed-adverse-effect level of CIT for offspring neurogenesis was determined to be 1 ppm, translating to 0.13-0.51 mg/kg body weight/day of maternal oral exposure. ..
  3. Abe H, Ogawa T, Wang L, Kimura M, Tanaka T, Morita R, et al. Promoter-region hypermethylation and expression downregulation of Yy1 (Yin yang 1) in preneoplastic liver lesions in a thioacetamide rat hepatocarcinogenesis model. Toxicol Appl Pharmacol. 2014;280:467-74 pubmed publisher
    ..These results suggest involvement of Yy1 in the epigenetic gene regulation at the early stages of TAA promoted cell proliferation and concomitant cell cycle arrest in preneoplastic lesions. ..
  4. Itahashi M, Abe H, Tanaka T, Mizukami S, Kimura M, Yoshida T, et al. Maternal exposure to hexachlorophene targets intermediate-stage progenitor cells of the hippocampal neurogenesis in rat offspring via dysfunction of cholinergic inputs by myelin vacuolation. Toxicology. 2015;328:123-34 pubmed publisher
  5. Tanaka T, Abe H, Kimura M, Onda N, Mizukami S, Yoshida T, et al. Developmental exposure to T-2 toxin reversibly affects postnatal hippocampal neurogenesis and reduces neural stem cells and progenitor cells in mice. Arch Toxicol. 2016;90:2009-24 pubmed publisher
    ..The no-observed-adverse-effect level for offspring neurogenesis was determined to be 1 ppm (0.14-0.49 mg/kg body weight/day). ..
  6. Hara S, Morita R, Shiraki A, Segawa R, Ogawa T, Takimoto N, et al. Expression of protein gene product 9.5 and Sal-like protein 4 in canine seminomas. J Comp Pathol. 2014;151:10-8 pubmed publisher
    ..This study was the first to show positive immunoreactivity for Sall4 in canine seminomas and dysgerminomas and expression of PGP9.5 in canine dysgerminomas. ..
  7. Tanaka T, Mizukami S, Hasegawa Baba Y, Onda N, Sugita Konishi Y, Yoshida T, et al. Developmental exposure of aflatoxin B1 reversibly affects hippocampal neurogenesis targeting late-stage neural progenitor cells through suppression of cholinergic signaling in rats. Toxicology. 2015;336:59-69 pubmed publisher
    ..The no-observed-adverse-effect level for offspring neurogenesis was determined to be 0.1 ppm (7.1-13.6 mg/kg body weight/day). ..
  8. Abe H, Tanaka T, Kimura M, Mizukami S, Imatanaka N, Akahori Y, et al. Developmental exposure to cuprizone reduces intermediate-stage progenitor cells and cholinergic signals in the hippocampal neurogenesis in rat offspring. Toxicol Lett. 2015;234:180-93 pubmed publisher
    ..However, all observed fluctuations disappeared at the adult stage, suggesting that CPZ-induced developmental neurotoxicity was reversible. ..
  9. Kikuchihara Y, Abe H, Tanaka T, Kato M, Wang L, Ikarashi Y, et al. Relationship between brain accumulation of manganese and aberration of hippocampal adult neurogenesis after oral exposure to manganese chloride in mice. Toxicology. 2015;331:24-34 pubmed publisher

More Information


  1. Tanaka T, Wang L, Kimura M, Abe H, Mizukami S, Yoshida T, et al. Developmental hypothyroidism abolishes bilateral differences in sonic hedgehog gene control in the rat hippocampal dentate gyrus. Toxicol Sci. 2015;144:128-37 pubmed publisher
  2. Kikuchihara Y, Onda N, Kimura M, Kangawa Y, Mizukami S, Yoshida T, et al. Induction of duodenal mucosal tumors of intestinal epithelial cell origin showing frequent nuclear β-catenin accumulation similar to the concurrently induced colorectal tumors in rats after treatment with azoxymethane. Exp Toxicol Pathol. 2015;67:349-53 pubmed publisher
    ..Similar to colorectal tumors, nuclear accumulation of β-catenin indicates activation of Wnt signaling as a driving force for tumor progression in AOM-induced duodenal tumors. ..
  3. Akane H, Shiraki A, Imatanaka N, Akahori Y, Itahashi M, Abe H, et al. Glycidol induces axonopathy and aberrations of hippocampal neurogenesis affecting late-stage differentiation by exposure to rats in a framework of 28-day toxicity study. Toxicol Lett. 2014;224:424-32 pubmed publisher
    ..These results suggest that glycidol causes aberrations in adult neurogenesis in the SGZ at the late stage involving the process of neurite extension similar to the developmental exposure study in a standard 28-day toxicity study. ..
  4. Abe H, Tanaka T, Kimura M, Mizukami S, Saito F, Imatanaka N, et al. Cuprizone decreases intermediate and late-stage progenitor cells in hippocampal neurogenesis of rats in a framework of 28-day oral dose toxicity study. Toxicol Appl Pharmacol. 2015;287:210-21 pubmed publisher
    ..The effects of postpubertal CPZ on neurogenesis were similar to those observed with developmental exposure, except for the lack of reelin response, which may contribute to a greater decrease in SGZ cells. ..
  5. Mizukami S, Murakami T, Tanaka T, Machida N, Nomura K, Yoshida T, et al. Spermatogonial Nature of the Germ Cell Component of Canine Testicular Mixed Germ Cell-Sex Cord Stromal Tumours. J Comp Pathol. 2016;155:5-14 pubmed publisher
    ..The results suggest that the germ cell component of canine MGSCTs is morphologically classified as SS, with the majority of cases showing the spermatogonial phenotype and some cases containing a small population of prespermatogonia. ..
  6. Shiraki A, Tanaka T, Watanabe Y, Saito F, Akahori Y, Imatanaka N, et al. Immunohistochemistry of aberrant neuronal development induced by 6-propyl-2-thiouracil in rats. Toxicol Lett. 2016;261:59-71 pubmed publisher
    ..In contrast, only hippocampal neurogenesis was sensitive to adult-stage exposure. ..
  7. Abe H, Saito F, Tanaka T, Mizukami S, Hasegawa Baba Y, Imatanaka N, et al. Developmental cuprizone exposure impairs oligodendrocyte lineages differentially in cortical and white matter tissues and suppresses glutamatergic neurogenesis signals and synaptic plasticity in the hippocampal dentate gyrus of rats. Toxicol Appl Pharmacol. 2016;290:10-20 pubmed publisher
    ..CPZ also reversibly targeted glutamatergic signals of GABAergic interneuron to affect dentate gyrus neurogenesis and synaptic plasticity in granule cells. ..
  8. Tanaka T, Hasegawa Baba Y, Watanabe Y, Mizukami S, Kangawa Y, Yoshida T, et al. Maternal exposure to ochratoxin A targets intermediate progenitor cells of hippocampal neurogenesis in rat offspring via cholinergic signal downregulation and oxidative stress responses. Reprod Toxicol. 2016;65:113-122 pubmed publisher
    ..All observed fluctuations were reversed by PND 77. The no-observed-adverse-effect level for offspring neurogenesis was determined to be 0.6ppm, corresponding to 39.3-76.0?g/kg body weight/day. ..
  9. Kimura M, Mizukami S, Watanabe Y, Onda N, Yoshida T, Shibutani M. Aberrant cell cycle regulation in rat liver cells induced by post-initiation treatment with hepatocarcinogens/hepatocarcinogenic tumor promoters. Exp Toxicol Pathol. 2016;68:399-408 pubmed publisher
    ..Four weeks of post-initiation treatment may be sufficient to induce hepatocarcinogen/tumor promoter-specific cellular responses. ..
  10. Abe H, Saito F, Tanaka T, Mizukami S, Watanabe Y, Imatanaka N, et al. Global gene expression profiles in brain regions reflecting abnormal neuronal and glial functions targeting myelin sheaths after 28-day exposure to cuprizone in rats. Toxicol Appl Pharmacol. 2016;310:20-31 pubmed publisher
  11. request reprint
    Nagahara R, Kimura M, Itahashi M, Sugahara G, Kawashima M, Murayama H, et al. Canine mammary minute oncocytomas with neuroendocrine differentiation associated with multifocal acinar cell oncocytic metaplasia. J Vet Diagn Invest. 2016;28:722-728 pubmed
    ..From these results, our case was diagnosed with mammary oncocytomas accompanied by neuroendocrine differentiation. Scattered foci of mammary oncocytosis might be related to the multicentric occurrence of these oncocytomas. ..
  12. Kaneko Y, Onda N, Watanabe Y, Shibutani M. Identification of 5-hydroxytryptamine-producing cells by detection of fluorescence in paraffin-embedded tissue sections. Eur J Histochem. 2016;60:2684 pubmed publisher
    ..This autofluorescence signal detection method may be applicable for monitoring of inflammatory status of inflammatory bowel diseases in both the experimental and clinical settings. ..
  13. Watanabe Y, Murakami T, Kawashima M, Hasegawa Baba Y, Mizukami S, Imatanaka N, et al. Maternal Exposure to Valproic Acid Primarily Targets Interneurons Followed by Late Effects on Neurogenesis in the Hippocampal Dentate Gyrus in Rat Offspring. Neurotox Res. 2017;31:46-62 pubmed publisher
    ..The late effect on neurogenesis, which resulted in increased GCL neurons, might be the result of a sustained decrease in GAD67+ interneurons expressing NR2D encoded by Grin2d. ..
  14. Mizukami S, Yafune A, Watanabe Y, Nakajima K, Jin M, Yoshida T, et al. Identification of epigenetically downregulated Tmem70 and Ube2e2 in rat liver after 28-day treatment with hepatocarcinogenic thioacetamide showing gene product downregulation in hepatocellular preneoplastic and neoplastic lesions produced by tumor pr. Toxicol Lett. 2017;266:13-22 pubmed publisher
  15. Hasegawa Baba Y, Tanaka T, Watanabe Y, Wang L, Itahashi M, Yoshida T, et al. Late Effect of Developmental Exposure to 3,3'-Iminodipropionitrile on Neurogenesis in the Hippocampal Dentate Gyrus of Mice. Neurotox Res. 2017;32:27-40 pubmed publisher
    ..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. ..
  16. Kawashima M, Watanabe Y, Nakajima K, Murayama H, Nagahara R, Jin M, et al. Late effect of developmental exposure to glycidol on hippocampal neurogenesis in mice: Loss of parvalbumin-expressing interneurons. Exp Toxicol Pathol. 2017;69:517-526 pubmed publisher
  17. Watanabe Y, Nakajima K, Mizukami S, Akahori Y, Imatanaka N, Woo G, et al. Differential effects between developmental and postpubertal exposure to N-methyl-N-nitrosourea on progenitor cell proliferation of rat hippocampal neurogenesis in relation to COX2 expression in granule cells. Toxicology. 2017;389:55-66 pubmed publisher
    ..Thus, the disrupted pattern of hippocampal neurogenesis induced by MNU is different between developmental and postpubertal exposure. ..
  18. Mizukami S, Watanabe Y, Saegusa Y, Nakajima K, Ito Y, Masubuchi Y, et al. Downregulation of UBE2E2 in rat liver cells after hepatocarcinogen treatment facilitates cell proliferation and slowing down of DNA damage response in GST-P-expressing preneoplastic lesions. Toxicol Appl Pharmacol. 2017;334:207-216 pubmed publisher
    ..Our results suggest that repeated hepatocarcinogen treatment of rats causes stabilization of UBE2E2-related ubiquitination target proteins in liver cells to promote carcinogenesis. ..
  19. Shiraki A, Saito F, Akane H, Takeyoshi M, Imatanaka N, Itahashi M, et al. Expression alterations of genes on both neuronal and glial development in rats after developmental exposure to 6-propyl-2-thiouracil. Toxicol Lett. 2014;228:225-34 pubmed publisher
    ..These results suggest that multifocal brain region-specific microarray analysis can determine the affection of neuronal or glial development. ..