Research Experience 【 display / non-display 】

Research Experience 【 display / non-display 】

• 2022.07

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  Now

  Sapporo Medical University   School of Health Sciences Department of Occupational Therapy   教授

Research Areas 【 display / non-display 】

Research Areas 【 display / non-display 】

• Life sciences   Psychiatry  

Affiliation 【 display / non-display 】

Affiliation 【 display / non-display 】

• Sapporo Medical University   School of Health Sciences Department of Occupational Therapy   教授  

Research Interests 【 display / non-display 】

Research Interests 【 display / non-display 】

• コンサルテーション・リエゾン精神医学

• 精神腫瘍学

• 慢性疼痛

• 精神薬理学

Papers 【 display / non-display 】

Papers 【 display / non-display 】

• Reduced sociability in a prenatal immune activation model: Modulation by a chronic blonanserin treatment through the amygdala-hippocampal axis.

  Kenta Deriha, Eri Hashimoto, Wataru Ukai, Francesca Marchisella, Emi Nishimura, Hanako Hashiguchi, Masaya Tayama, Takao Ishii, Marco A Riva, Chiaki Kawanishi

  Journal of psychiatric research   164   209 - 220  2023.08  [International journal]

  　View Summary

  The environmental disturbances in a critical neurodevelopmental period exert organizational effects on brain intrinsic plasticity including excitatory and inhibitory (E/I) neurotransmission those can cause the onset of psychiatric illness. We previously reported that treatment of neural precursor cells with N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 induced reduction of GABAergic interneuron differentiation, and these changes recovered by atypical antipsychotic blonanserin treatment in vitro. However, it remains unclear how this treatment affects neural circuit changes in hippocampus and amygdala, which might contribute to the prevention of onset process of schizophrenia. To elucidate the pathogenic/preventive mechanisms underlying prenatal environmental adversity-induced schizophrenia in more detail, we administered poly (I:C) followed by antipsychotics and examined alterations in social/cognitive behaviors, GABA/glutamate-related gene expressions with cell density and E/I ratio, and brain-derived neurotrophic factor (Bdnf) transcript levels, particularly in limbic areas. Treatment with antipsychotic blonanserin ameliorated impaired social/cognitive behaviors and increased parvalbumin (PV)-positive (+) cell density and its mRNA levels as well as Bdnf with long 3'UTR mRNA levels, particularly in the dorsal hippocampus, in rats exposed to maternal immune activation (MIA). Low dose of blonanserin and haloperidol altered GABA and glutamate-related mRNA levels, the E/I ratio, and Bdnf long 3'UTR mRNA levels in the ventral hippocampus and amygdala, but did not attenuate behavioral impairments. These results strongly implicate changes in PV expression, PV(+) GABAergic interneuron density, and Bdnf long 3'UTR expression levels, particularly in the dorsal hippocampus, in the pathophysiology and treatment responses of MIA-induced schizophrenia and highlight the therapeutic potential of blonanserin for developmental stress-related schizophrenia.

  DOI PubMed

• Implementations of an evidence‐based assertive case management intervention for suicide attempters: Post‐ACTION‐J Study (PACS)

  Takao Ishii, Naohiro Yonemoto, Yasushi Otaka, Kazuya Okamura, Noa Tsujii, Kotaro Otsuka, Reiji Yoshimura, Toshihiko Kinoshita, Daisuke Fujisawa, Hirokazu Tachikawa, Mitsuhiko Yamada, Yusuke Tsuyama, Satoshi Hashimoto, Chiaki Kawanishi

  Psychiatry and Clinical Neurosciences Reports    2023.06

  DOI

• Identification of epigenetically active L1 promoters in the human brain and their relationship with psychiatric disorders.

  Risa Watanabe, Yutaka Nakachi, Hikari Matsubara, Junko Ueda, Takao Ishii, Wataru Ukai, Eri Hashimoto, Kiyoto Kasai, Siro Simizu, Tadafumi Kato, Miki Bundo, Kazuya Iwamoto

  Neuroscience research    2023.05  [International journal]

  　View Summary

  Long interspersed nuclear element-1 (LINE-1, L1) affects the transcriptome landscape in multiple ways. Promoter activity within its 5'UTR plays a critical role in regulating diverse L1 activities. However, the epigenetic status of L1 promoters in adult brain cells and their relationship with psychiatric disorders remain poorly understood. Here, we examined DNA methylation and hydroxymethylation of the full-length L1s in neurons and nonneurons and identified "epigenetically active" L1s. Notably, some of epigenetically active L1s were retrotransposition competent, which even had chimeric transcripts from the antisense promoters at their 5'UTRs. We also identified differentially methylated L1s in the prefrontal cortices of patients with psychiatric disorders. In nonneurons of bipolar disorder patients, one L1 was significantly hypomethylated and showed an inverse correlation with the expression level of the overlapping gene NREP. Finally, we observed that altered DNA methylation levels of L1 in patients with psychiatric disorders were not affected by the surrounding genomic regions but originated from the L1 sequences. These results suggested that altered epigenetic regulation of the L1 5'UTR in the brain was involved in the pathophysiology of psychiatric disorders.

  DOI PubMed

• 統合失調症の社会性認知機能障害の脳基盤解析 Glutamate/GABAニューロンバランスメカニズムからの検討

  出利葉 健太, 鵜飼 渉, Riva Marco, 西村 恵美, 橋本 恵理, 木川 昌康, 橋口 華子, 古瀬 研吾, 田山 真矢, 村山 友規, 石井 貴男, 河西 千秋

  日本神経精神薬理学会年会・日本生物学的精神医学会年会・日本精神薬学会総会・学術集会合同年会プログラム・抄録集 ( 日本神経精神薬理学会・日本生物学的精神医学会・日本精神薬学会 )  50回・42回・4回   189 - 189  2020.08

• 胎生期免疫ストレス誘発統合失調症モデルの社会性行動とGABA作動性インターニューロン変化に関する研究

  橋本 恵理, 鵜飼 渉, 西村 恵美, 橋口 華子[辻野], 木川 昌康, 田山 真矢, 出利葉 健太, 廣瀬 奨真, 古瀬 研吾, 石井 貴男, 河西 千秋

  精神神経学雑誌 ( (公社)日本精神神経学会 )  ( 2019特別号 ) S470 - S470  2019.06

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Misc 【 display / non-display 】

Misc 【 display / non-display 】

• 自殺未遂者へのアサーティヴ・ケースマネジメントの実装 多施設共同コホート研究

  石井 貴男, 米本 直裕, 大高 靖史, 岡村 和哉, 辻井 農亜, 大塚 耕太郎, 吉村 玲児, 木下 利彦, 藤澤 大介, 太刀川 弘和, 山田 光彦, 津山 雄亮, 橋本 聡, 河西 千秋

  総合病院精神医学 ( (一社)日本総合病院精神医学会 )  35 ( Suppl. ) S - 166  2023.11

• 皮膚寄生虫妄想を呈したレビー小体型認知症の1例

  姜 撤求, 大江 開, 野呂 孝徳, 石井 貴男, 河西 千秋

  精神神経学雑誌 ( (公社)日本精神神経学会 )  124 ( 12 ) 894 - 894  2022.12

• 性欲の異常亢進と誤診されていたrestless genital syndromeの1例

  廣瀬 奨真, 大江 開, 野呂 孝徳, 石井 貴男, 河西 千秋

  精神神経学雑誌 ( (公社)日本精神神経学会 )  124 ( 12 ) 894 - 894  2022.12

• 札幌医科大学附属病院高度救命救急センターに搬送された自殺企図事例の実態調査

  石橋 竜太朗, 佐野 智章, 大江 開, 津山 雄亮, 岩木 敦子, 昌川 安希子, 柏木 智則, 古俣 皓涼, 石井 貴男, 河西 千秋

  総合病院精神医学 ( (一社)日本総合病院精神医学会 )  34 ( Suppl. ) S - 163  2022.10

• がん患者の自殺予防を目的としたケース・マネジメント介入 フィジビリティ研究

  石井 貴男, 岩木 敦子, 津山 雄亮, 菅原 夏海, 成田 賢治, 大江 開, 佐野 智章, 河西 千秋

  総合病院精神医学 ( (一社)日本総合病院精神医学会 )  34 ( Suppl. ) S - 186  2022.10

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Research Projects 【 display / non-display 】

Research Projects 【 display / non-display 】

• 血小板のBDNF放出能の変化に着目した慢性疼痛とうつ病のバイオマーカー開発

  基盤研究(C)

  Project Year :

  2022.04

  -

  2025.03

   

  石井 貴男

• Recovery of occupational functions in schizophrenia: significance of empathy behavior enhancement by synchronizer neuron activation

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2022.04

  -

  2025.03

   

  鵜飼 渉, 仲地 ゆたか, 橋本 恵理, 石井 貴男, 館農 勝, 森元 隆文

• Neural basis of recovery of social cognitive impairment in mental disorder: significance of enhancing for synchronizer neurons

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2019.04

  -

  2022.03

   

  Ukai Wataru

  　View Summary

  First, we used animal model of schizophrenia produced by exposing rats to poly (I:C) during fetal period. We showed that treatment with a drug that has been reported to improve occupational and social dysfunction in schizophrenic patients in clinical practice recovered social behavior deficits in this model, involving the mechanism of increase in the number of parvalbumin (PV)-positive cells in the hippocampus and amygdala. Next, we conducted analysis of the molecular changes in the social/cognitive recovery, and found that treatment with the therapeutic drug increased PV and Bdnf long 3'UTR mRNA levels in the dorsal hippocampus, and that these were strongly implicated in the onset, pathogenesis, and treatment response of developmental stress-related schizophrenia.

• Social function recovery in schizophrenia: brain mechanism of empathy/concerning function using stem cells and oxytocin

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2014.04

  -

  2017.03

   

  Ukai Wataru, Iwamoto Kazuya, Morimoto Takafumi

  　View Summary

  First, we analyzed the social functioning behavior of model animals administered with stem cells and the distribution of cells in the brain. We detected that the patient-derived stem cells was difficult to become GAD67 and Parvalbumin-positive GABA interneurons in the brain after administration, and social interaction behavior was decreased in the patient-derived stem cell administered group compared to the control and healthy-derived stem cell administered group. Next, the synapse forming ability of the GABAergic interneuron was analyzed by the actin motility of the precursor structure filopodia, and found the reduction of the filopodia movement in the patient-derived cells. We also found that the possibility of the influence of decreased expression of the transcription factor TBX1 against it.

• The develpoment of biological marker for alcohol-induced mood disorders: focusing on the functional alteration of platelet and neural stem cell

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2013.04

  -

  2016.03

   

  ISHII Takao, HASHIMOTO ERI, MATSUYAMA KIYOJI, UKAI WATARU, SOUMA HITOSHI

  　View Summary

  In this study, we investigated the common pathophysiology of alcohol-induced brain damage and mood disorders, focusing on the functional alteration of platelet and neural stem cell. We examine the effects of ethanol and antidepressants on the platelet BDNF release. Ethanol suppressed platelet BDNF release and the promotive effect of antidepressant on BDNF release. Furthermore, we investigated the transfer of BDNF derived from serum (or platelet) to the brain using fluorescent-labeled BDNF. We have detected BDNF-FITC in the cells at dentate gyrus in the hippocampus in which adult neurogenesis occurs.

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