Study on mood disorder pathogenesis using a novel animal model of bipolar disorders expressing protein of human herpesvirus.

• Project/Area Number: 23791355
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Psychiatric science
• Research Institution: Jikei University School of Medicine
• Principal Investigator: KOBAYAHI Nobuyuki 東京慈恵会医科大学, 医学部, 助教 (20385321)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 双極性障害 / 気分障害 / ヒトヘルペスウイルス6 / SITH-1 / 動物モデル / 炎症性サイトカイン / BDNF / うつ病 / HHV-6 / ヒトヘルペスウイルス６

Research Abstract

Small protein encoded by the Intermediate stage Transcript of Human herpesvirus (HHV-)6 (SITH) -1, a latent transcript of HHV-6, causes depressive-like behavior by being expressed in mouse astrocytes. Inflammatory cytokine mRNA levels did not change in the brains of mice. On the other hand, inflammatory cytokine mRNA blood levels and depressive symptom severity were correlated with mood disorders in human patients. Gene expression in peripheral blood and the central nervous system (CNS) do not necessarily coincide. Systemic inflammation affects the CNS and induction of SITH-1 may cause depressive symptoms.

Research Products

• [Journal Article] Plasma BDNF levels are correlated with aggressiveness in patients with amnestic mild cognitive impairment or Alzheimer disease. (2014)
  • Author(s): Tomoyuki Nagata, Nobuyuki Kobayashi, Shunichiro Shinagawa, Hisashi Yamada, Kazuhiro Kondo, and Kazuhiko Nakayama
  • Journal Title: Journal of Neural Transmission Volume: 121 Issue: 4 Pages: 433-441
  • DOI: 10.1007/s00702-013-1121-y
  • Peer Reviewed
• [Journal Article] Novel gene therapy viral vector using non-oncogenic lymphotropic herpesvirus. (2013)
  • Author(s): Shimizu A, Kobayashi N, Shimada K, Oura K, Tanaka T, Okamoto A, Kondo K.
  • Journal Title: PLoS One Volume: 8 Issue: 2 Pages: e56027-e56027
  • DOI: 10.1371/journal.pone.0056027
  • Peer Reviewed
• [Journal Article] Increase in the IgG avidity index due to herpes simplex virus type 1 reactivation and its relationship with cognitive function in amnestic mild cognitive impairment and Alzheimer's disease. (2013)
  • Author(s): Kobayashi N
  • Journal Title: Biochem Biophys Res Commun Volume: 430 Issue: 3 Pages: 907-11
  • DOI: 10.1016/j.bbrc.2012.12.054
  • Peer Reviewed
• [Journal Article] 新規組み換えヒトヘルペスウイルス6B(HHV-6B)を用いたHHV-6Bゲノム組み込み293T細胞の樹立とヒトゲノムDNAへの組み込み機構の解析 (2013)
  • Author(s): 清水昭宏、小林伸行、嶋田和也、近藤一博
  • Journal Title: 東京慈恵会医科大学雑誌 Volume: 128巻(1号) Pages: 41-52
  • NAID: 120005260142
  • URL: http://hdl.handle.net/10328/7746
  • Peer Reviewed
• [Journal Article] Association between Neurotrophin-3 Polymorphisms and Executive Function in Japanese Patients with Amnestic Mild Cognitive Impairment and Mild Alzheimer Disease (2012)
  • Author(s): Kobayashi N, Nagata T, Shinagawa S, Nakayama R, Kond K, Nakayama K, Yamada H.
  • Journal Title: Dement Geriatr Cogn Disord Volume: 34 Issue: 3-4 Pages: 190-197
  • DOI: 10.1159/000343075
  • Peer Reviewed
• [Journal Article] 精神科領域から見た疼痛ー身体表現性障害と慢性疲労症候群ー (2012)
  • Author(s): 小林伸行 中山和彦 近藤一博
  • Journal Title: 女性心身医学 Volume: 16 Pages: 251-255
• [Journal Article] 改良型遺伝子濃縮法によるヒトヘルペスウイルス6の前初期遺伝子および新規潜伏感染特異的遺伝子の同定 (2011)
  • Author(s): 小川智生、川嶋公成、清水昭宏、小林伸行、近藤一博
  • Journal Title: 東京慈恵会医科大学雑誌 Volume: 126(1) Pages: 1-10
  • NAID: 120003072812
  • URL: http://hdl.handle.net/10328/6567
  • Peer Reviewed
• [Presentation] アルツハイマー型認知症の前駆段階において単純ヘルペスウイルス1型再活性化が発症に与える影響 (2013)
  • Author(s): 小林伸行、岡直美、嶋田和也、近藤一博
  • Organizer: 第61回日本ウイルス学会
  • Place of Presentation: 神戸
  • Year and Date: 2013-11-10
• [Presentation] 疲労・ストレスによるヒトヘルペスウイルス(HHV-)6、7再活性化機構の検討 (2012)
  • Author(s): 小林伸行、鈴木豪、徳野慎一、山本泰輔、波多野弁、清水昭宏、嶋田和也、立花正一、近藤一博
  • Organizer: 第60回日本ウイルス学会
  • Place of Presentation: 大阪
  • Year and Date: 2012-11-13
• [Presentation] Identification of SITH-1 as novel latent protein of Human Herpesvirus 6 (HHV-6) associated with chronic fatigue syndrome (CFS) and mood disorders (2011)
  • Author(s): Kobayashi N, Shimada K, Shimizu A, Kondo K.
  • Organizer: International Union of Microbiological Societies (IUMS) 2011 Congress
  • Place of Presentation: Sapporo
  • Year and Date: 2011-09-15
• [Presentation] 精神科領域から見た疼痛-身体表現性障害と慢性疲労症候群- (2011)
  • Author(s): 小林伸行
  • Organizer: 第40回日本女性心身医学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2011-07-24
• [Presentation] 精神科領域から見た疼痛-身体表現性障害と慢性疲労症候群- (2011)
  • Author(s): 小林伸行
  • Organizer: 第40回日本女性心身医学会学術集会(招待講演)
  • Place of Presentation: 東京
• [Presentation] Identification of SITH-1 as novel latent protein of Human Herpesvirus 6 (HHV-6) associated with chronic fatigue syndrome (CFS) and mood disorders. (2011)
  • Author(s): Nobuyuki Kobayashi, Kazuya Shimada, Akihiro Shimizu, Kazuhiro Kondo
  • Organizer: International Union of Microbiological Societies (IUMS) 2011 Congress
  • Place of Presentation: Sapporo
• [Presentation] アルツハイマー型認知症の前駆段階において単純ヘルペスウイルス1型再活性化が発症に与える影響
  • Author(s): 小林 伸行、岡 直美、嶋田 和也、近藤 一博
  • Organizer: 第61回日本ウイルス学会
  • Place of Presentation: 神戸
• [Presentation] 疲労・ストレスによるヒトヘルペスウイルス(HHV-)6、7再活性化機構の検討.
  • Author(s): 小林 伸行、鈴木 豪、徳野 慎一、山本 泰輔、波多野 弁、清水 昭宏、嶋田 和也、立花 正一、近藤 一博
  • Organizer: 第60回日本ウイルス学会
  • Place of Presentation: 大阪