ROLE OF TRANSCRIPTION FACTOR NPAS4 IN DRUG DEPENDENCE

• Project/Area Number: 23790081
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: Nagoya University
• Principal Investigator: NAGAI Taku 名古屋大学, 医学部附属病院, 准教授 (10377426)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 薬物依存 / 転写因子 / メタンフェタミン

Research Abstract

It has been proposed that activity-dependent synaptic plasticity and remodeling of the mesolimbic dopaminergic system play a crucial role in the development of drug dependence. We previously reported that reduced Npas4 mRNA levels might contribute to impairments in memory and emotional behaviors induced by social isolation or restriction stress. In this study,we investigated pathophysiological role of NPAS4 in the drug dependence. Our results suggest that Npas4 plays an important role in the structural and functional plasticity of neurons. In addition, we assume that repeated administration of methamphetamine increases the expression levels of Npas4 in the hippocampus.

Research Products

• [Journal Article] Neuronal PAS domain protein 4 (Npas4) regulates neurite outgrowth and phosphorylation of synapsin I (2013)
  • Author(s): Yun, J., Nagai, T., Furukawa-Hibi, Y., Kuroda, K., Kaibuchi, K., Greenberg, M.E., Yamada, K
  • Journal Title: J. Biol. Chem Volume: 288 Pages: 2655-2664
  • Peer Reviewed
• [Journal Article] Astroglial IFITM3 mediates neuronal impairments following neonatal immune challenge in mice (2013)
  • Author(s): Ibi, D., Nagai, T., Nakajima, A., Mizoguchi, H., Kawase, T., Tsuboi, D., Kano, S.I., Sato, Y., Hayakawa, M., Lange, U.C., Adams, D.J., Surani, M.A., Satoh, T., Sawa, A., Kaibuchi, K., Nabeshima, T., Yamada, K
  • Journal Title: Glia Volume: 61 Pages: 679-693
  • Peer Reviewed
• [Journal Article] Neuronal PAS domain domain protein 4 (Npas4) regulates neurite outgrowth and phosphorylation of synapsin I. (2013)
  • Author(s): Yun J, Nagai T, Furukawa-Hibi Y, Kuroda K, Kaibuchi K, Greenberg ME, and Yamada K
  • Journal Title: J. Biol. Chem. Volume: 288 Issue: 4 Pages: 2655-2664
  • DOI: 10.1074/jbc.m112.413310
  • Peer Reviewed
• [Journal Article] Prenatal NMDA receptor antagonism impaired proliferation of neuronal progenitor, leading to fewer glutamatergic neurons in the prefrontal cortex (2012)
  • Author(s): Toriumi, K., Mouri, A., Narusawa, S., Aoyama, Y., Ikawa, N., Lu, L., Nagai, T., Mamiya, T., Kim, H.C., Nabeshima, T
  • Journal Title: Neuropsychopharmacology Volume: 37 Pages: 1387-1396
  • Peer Reviewed
• [Journal Article] Combination of chronic stress and ovariectomy causes conditioned fear memory deficits and hippocampal cholinergic neuronal loss in mice (2012)
  • Author(s): Takuma, K., Mizoguchi, H., Funatsu, Y., Hoshina, Y., Himeno, Y., Fukuzaki, E., Kitahara, Y., Arai, S., Ibi, D., Kamei, H., Matsuda, T., Koike, K., Inoue, M., Nagai, T., Yamada, K
  • Journal Title: Neuroscience Volume: 207 Pages: 261-273
  • Peer Reviewed
• [Journal Article] Placental extract improves hippocampal neuronal loss and fear memory impairment resulting from chronic restraint stress in ovariectomized mice (2012)
  • Author(s): Takuma, K., Mizoguchi, H., Funatsu, Y., Kitahara, Y., Ibi, D., Kamei, H., Matsuda, T., Koike, K., Inoue, M., Nagai, T., Yamada, K
  • Journal Title: J. Pharmacol. Sci Volume: 120 Pages: 89-97
  • NAID: 10031123550
  • Peer Reviewed
• [Journal Article] Transcriptional suppression of the neuronal PAS domain 4 (Npas4) gene by stress via the binding of agonist-bound glucocorticoid receptor to its promoter (2012)
  • Author(s): Furukawa-Hibi, Y., Yun, J., Nagai, T., Yamada, K
  • Journal Title: J. Neurochem Volume: 123 Pages: 866-875
  • Peer Reviewed
• [Journal Article] D-serine ameliorates neonatal polyI:C treatment-induced emotional and cognitive impairments in adult mice (2012)
  • Author(s): Nagai, T., Yu, J., Kitahara, Y., Nabeshima T., Yamada, K
  • Journal Title: J. Pharmacol. Sci Volume: 120 Pages: 213-227
  • NAID: 10031147568
  • Peer Reviewed
• [Journal Article] Effects of sub-acute and sub-chronic inhalation of 1-bromopropane on neurogenesis in adult rats (2012)
  • Author(s): Zhang, L., Nagai, T., Yamada, K., Ibi, D., Ichihara, S., Subramanian, K., Huang, Z., Mohideen, S.S., Naito, H., Ichihara G
  • Journal Title: Toxicology Volume: 304C Pages: 76-82
  • Peer Reviewed
• [Journal Article] Transcriptional suppression of the neuronal PAS domain 4 (Npas4) gene by stress via the binding of agonist-bound glucocorticoid receptor to its promoter (2012)
  • Author(s): Furukawa-Hibi Y, Yun J, Nagai T, and Yamada K
  • Journal Title: J Neurochem Volume: 123 Issue: 5 Pages: 866-875
  • DOI: 10.1111/jnc.12034
  • Peer Reviewed
• [Journal Article] Prenatal NMDA Receptor Antagonism Impaired Proliferation of Neuronal Progenitor, Leading to Fewer Glutamatergic Neurons in the Prefrontal Cortex (2012)
  • Author(s): Toriumi K, et al
  • Journal Title: Neuropsychopharmacology Volume: (In press) Issue: 6 Pages: 1387-1396
  • DOI: 10.1038/npp.2011.324
  • Peer Reviewed
• [Journal Article] Effects of antipsychotics on the behavioral deficits in human dominant-negative DISC1 transgenic mice with neonatal polyI:C treatment (2011)
  • Author(s): Nagai, T., Kitahara, Y., Ibi, D., Nabeshima, T., Sawa, A., Yamada, K
  • Journal Title: Behav. Brain Res Volume: 225 Pages: 305-310
  • Peer Reviewed
• [Journal Article] Behavioral alterations associated with targeted disruption of exons 2 and 3 of the DISC1 gene in the mouse (2011)
  • Author(s): Kuroda, K., Yamada, S., Tanaka, M., Iizuka, M., Yano, H., Mori, D., Tsuboi, D., Nishioka, T., Namba, T., Iizuka, Y., Kubota, S., Nagai, T., Ibi, D., Wang, R., Enomoto, A., Isotani-Sakakibara,M., Asai, N., Kimura, K., Kiyonari, H., Abe, T., Mizoguchi, A., Sokabe, M., Takahashi, M., Yamada, K., Kaibuchi, K
  • Journal Title: Hum. Mol. Genet Volume: 20 Pages: 4666-4683
  • Peer Reviewed
• [Journal Article] Exposure to enriched environments during adolescence prevents abnormal behaviours associated with histone deacetylation in phencyclidine-treated mice (2011)
  • Author(s): Koseki, T., Mouri, A., Mamiya, T., Aoyama, Y., Toriumi, K., Suzuki, S., Nakajima, A., Yamada, T., Nagai, T., Nabeshima, T
  • Journal Title: Int. J. Neuropsychopharmacol Volume: 18 Pages: 1-13
  • Peer Reviewed
• [Journal Article] Butyrylcholinesterase inhibitors ameliorate cognitive dysfunction induced by amyloid-β peptide in mice. (2011)
  • Author(s): Furukawa-Hibi, Y, Alkam, T., Nitta, A., Matsuyama, A., Mizoguchi, H., Suzuki, K., Moussaoui, S., Yu, Q-S., Greig, N.H., Nagai, T., Yamada, K.
  • Journal Title: Behav. Brain Res. Volume: 225 Pages: 222-229
  • Peer Reviewed
• [Journal Article] Effects of antipsychotics on the behavioral deficits in human dominant-negative DISC1 transgenic mice with neonatal polyI:C treatment. (2011)
  • Author(s): Nagai, T., Kitahara, Y., Ibi, D., Nabeshima, T., Sawa, A., Yamada, K.
  • Journal Title: Behav. Brain Res. Volume: 225 Pages: 305-310
  • Peer Reviewed
• [Journal Article] Behavioral alterations associated with targeted disruption of exons 2 and 3 of the DISC1 gene in the mouse. (2011)
  • Author(s): Kuroda, K., Yamada, S., Tanaka, M., et al.
  • Journal Title: Hum. Mol. Genet. Volume: 20 Pages: 4666-4683
  • Peer Reviewed
• [Journal Article] Exposure to enriched environments during adolescence prevents abnormal behaviours associated with histone deacetylation in phencyclidine-treated mice. (2011)
  • Author(s): Koseki, T., Mouri, A., Mamiya, T., Aoyama, Y., Toriumi, K., Suzuki, S., Nakajima, A., Yamada, T., Nagai, T., Nabeshima, T.
  • Journal Title: Int. J. Neuropsychopharmacol. Volume: 18 Pages: 1-13
  • Peer Reviewed
• [Presentation] 精神疾患モデル動物を用いた神経精神薬理学的研究 (特別講演) (2012)
  • Author(s): 永井拓
  • Organizer: 第16回日本神経麻酔・集中治療研究会
  • Place of Presentation: 岡山,岡山コンベンションセンター/岡山大学
• [Presentation] ドパミン作動性およびグルタミン酸作動性神経伝達の変調と障害に関する神経精神薬理学的研究 (日本神経精神薬理学会 2012 年 第1回学術奨励賞受賞講演) (2012)
  • Author(s): 永井拓
  • Organizer: 第22回日本臨床精神神経薬理学会・第42回日本神経精神薬理学会合同年会
  • Place of Presentation: 宇都宮,栃木県総合文化センター/宇都宮東武ホテルグランデ
• [Presentation] 精神疾患モデル動物を用いた神経精神薬理学的研究 (2012)
  • Author(s): 永井拓
  • Organizer: 第16回日本神経麻酔・集中治療研究会
  • Place of Presentation: 岡山コンベンションセンター（岡山）
  • Invited
• [Presentation] 新生仔期polyI:C処置による神経発達障害にはアストロサイトのIFITM3が関与している (2012)
  • Author(s): 永井拓, 鍋島俊隆, 山田清文
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋国際会議場（名古屋）
• [Presentation] ドパミン作動性およびグルタミン酸作動性神経伝達の変調と障害に関する神経精神薬理学的研究 (2012)
  • Author(s): 永井拓
  • Organizer: 第22回日本臨床精神神経薬理学会・第42回日本神経精神薬理学会合同年会
  • Place of Presentation: 栃木県総合文化センター
  • Invited
• [Presentation] 周産期免疫異常応答によって惹起される精神発達障害とそのメカニズム (2012)
  • Author(s): 永井拓, 衣斐大祐, 山田真之亮, 山田清文
  • Organizer: 第85回日本薬理学会年会
  • Place of Presentation: 国立京都国際会館（ 京都府 ）
• [Presentation] 統合失調症モデル動物を用いたプロテオーム解析 (2012)
  • Author(s): 永井拓, 山田清文, 鍋島俊隆
  • Organizer: 第7回日本統合失調症学会
  • Place of Presentation: ウインクあいち（ 愛知県 ）
• [Presentation] 神経精神発達に対する幼若期ストレスの影響 (2011)
  • Author(s): 永井拓, 尹錫在, 日比陽子, 山田清文
  • Organizer: 第54回日本神経化学会大会
  • Place of Presentation: 加賀, 瑠璃光
• [Presentation] プロテアーゼを介した薬物依存形成の神経化学的機序 (2011)
  • Author(s): 永井拓
  • Organizer: 第21回日本臨床精神神経薬理学会・第41回日本神経精神薬理学会合同年会
  • Place of Presentation: 東京,京王プラザホテル
• [Presentation] 周産期における異常免疫応答と神経発達障害 (2011)
  • Author(s): 永井拓
  • Organizer: 第21回日本臨床精神神経薬理学会・第41回日本神経精神薬理学会合同年会
  • Place of Presentation: 東京,京王プラザホテル
• [Presentation] Npas4 regulates neurite outgrowth and phosphorylation of synapsinI (2011)
  • Author(s): 尹錫在, 永井拓, 日比陽子, 黒田啓介, 貝淵弘三, 山田清文
  • Organizer: 第21回日本臨床精神神経薬理学会・第41回日本神経精神薬理学会合同年会
  • Place of Presentation: 東京,京王プラザホテル
• [Presentation] 遺伝子―環境相互作用に基づいた統合失調症モデル動物における抗精神病薬の効果. (2011)
  • Author(s): 永井拓, 北原裕子, 衣斐大祐, 鍋島俊隆, 澤明, 山田清文.
  • Organizer: 第57回日本薬学会東海支部総会・大会
  • Place of Presentation: 金城学院大学（ 愛知県 ）
• [Presentation] 神経精神発達に対する幼若期ストレスの影響 (2011)
  • Author(s): 永井拓, 尹錫在, 日比陽子, 山田清文
  • Organizer: 第54回日本神経化学会大会
  • Place of Presentation: 瑠璃光（ 石川県 ）
• [Presentation] プロテアーゼを介した薬物依存形成の神経化学的機序 (2011)
  • Author(s): 永井拓.
  • Organizer: 第21回日本臨床精神神経薬理学会・第41回日本神経精神薬理学会合同年会
  • Place of Presentation: 京王プラザホテル（ 東京都 ）
• [Presentation] 周産期における異常免疫応答と神経発達障害 (2011)
  • Author(s): 永井拓
  • Organizer: 第21回日本臨床精神神経薬理学会・第41回日本神経精神薬理学会合同年会
  • Place of Presentation: 京王プラザホテル（ 東京都 ）
• [Remarks]
  • URL: http://www.med.nagoya-u.ac.jp/pharmacy/02/index.html
• [Remarks] 名古屋大学大学院医学系研究科医療薬学ホームページ
  • URL: http://www.med.nagoya-u.ac.jp/pharmacy/02/index.html