Evaluation of involvement of anti-aquaporin 4 and CSF histamin levels in secondary hypersomnia

• Project/Area Number: 25860985
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Psychiatric science
• Research Institution: Akita University
• Principal Investigator: SAGAWA Yohei 秋田大学, 医学(系)研究科(研究院), 助教 (10637565)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: ナルコレプシー / オレキシン / アクアポリン４ / ヒスタミン / アクアポリン4

Outline of Final Research Achievements

(1) We examined the clinical symptoms and CSF orexin levels in the secondary hypersomnia that have a lesion in the hypothalamus. CSF orexin levels of all cases in this study were low or intermediate values. Then in all case, CSF orexin levels were recovered to normal level after treatment.Since AQP4 is highly expressed in the hypothalamic periventricular regions, an immune attack on AQP4 may be partially responsible for the bilateral and hypothalamic lesions and orexin deficiency in narcolepsy/EDS associated with autoimmune demyelinating diseases.
(2) We have further estimated the histamine in CSF of several neurological diseases such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Average histamine value was low in PSP and CBD compared to the MSA. This may suggest that the hypersomnia symptom in PSP is more severe compared to the MSA.

Research Products

• [Journal Article] Noninvasive detection of sleep/wake changes and cataplexy-like behaviors in orexin/ataxin-3 transgenic narcoleptic mice across the disease onset. (2014)
  • Author(s): Sato M, Sagawa Y, Hirai N, Sato S, Okuro M, Kumar S, Kanbayashi T, Shimizu T, Sakai N, Nishino S.
  • Journal Title: Exp Neurol. Volume: 261 Pages: 744-751
  • DOI: 10.1016/j.expneurol.2014.08.004
  • Peer Reviewed
• [Journal Article] Association between heart rate variability, blood pressure and autono mic activityin cyclic alternating pattern during sleep. (2014)
  • Author(s): Kondo H, Ozone M, Ohki N, Nishino S, Shimizu T.etc.
  • Journal Title: Sleep. Volume: 37(1) Issue: 1 Pages: 187-94
  • DOI: 10.5665/sleep.3334
  • Peer Reviewed
• [Journal Article] SYMPATHETIC AND PARASYMPATHETIC CONTROL OF HEART RATE RESPONSE TO RESTRAINT STRESS DURING THE VULNERABLE PERIOD IN NEWBORN RATS. (2013)
  • Author(s): Tokunaga J, Sato S, Kanbayashi T, Imanishi A, Sagawa Y, Sato M, Sakai N, Nishino S, Shimizu T.
  • Journal Title: Akita J. Med. Volume: 40(2) Pages: 89-103
  • NAID: 110009658221
  • Peer Reviewed
• [Journal Article] 最新臨床睡眠学 睡眠障害の基礎と臨床 中枢性過眠症候群 ナルコレプシー. (2013)
  • Author(s): 佐川洋平, 神林崇
  • Journal Title: 日本臨牀 Volume: 71 Pages: 363-369
• [Journal Article] Histamine from brain resident mast cells promotes wakefulness and modulates behavioral states (2013)
  • Author(s): Chikahisa S, Kodama T, Soya A, Sagawa Y, Ishimaru Y, Sei H, Nishino S
  • Journal Title: PLoS One Volume: 8 Issue: 10 Pages: e78434-e78434
  • DOI: 10.1371/journal.pone.0078434
  • Peer Reviewed
• [Presentation] Noninvasive detection of sleep/wake changes in orexin/ataxin-3 transgenic narcoleptic mice across the disease onset (2014)
  • Author(s): Y. Sagawa, M. Sato, S. Sato, A. Imanishi, T. Kanbayashi,T. Shimizu1 and S. Nishino
  • Organizer: the 22nd Congress of the European Sleep Research Society
  • Place of Presentation: Tallinn, Estonia
  • Year and Date: 2014-09-16 – 2014-09-20
• [Presentation] Orexin levels in patients with Niemann-Pick type C and their response to Miglustat treatment (2014)
  • Author(s): Y. Sagawa, T. Kanbayashi, H. Kubota, Y. Hamada,A. Imanishi, M. Omokawa T. Takahashi, N. Sakai, S. Nishino, T. Shimizu
  • Organizer: the 22nd Congress of the European Sleep Research Society
  • Place of Presentation: Tallinn, Estonia
  • Year and Date: 2014-09-16 – 2014-09-20
• [Presentation] THE INTERVENTION OF OREXIN SYSTEM IN PARKINSON’S DISEASE AND PROGRESSIVE SUPRANUCLEAR PALSY WITH HYPERSOMNIA (2014)
  • Author(s): Takahashi Y, Imanishi A, Tokunaga J, Sagawa Y, Takanashi M, Aburakawa Y, Hattori Y, Kanbayashi T, Shimizu T.
  • Organizer: the 28th Annual Meeting of the APSS
  • Place of Presentation: Minneapolis, MN
  • Year and Date: 2014-05-31 – 2014-06-04
• [Presentation] CSF NEUROENDOCRINE REGULATORY PEPTIDE (NERP)-2 LEVELS ARE POSITIVELY CORRELATED WITH OREXIN (HYPOCRETIN) LEVELS. (2014)
  • Author(s): Kanbayashi T, Imanishi A, Sagawa Y, Inomata Y, Uemura-Ito S, Sato M, Takeshima M, Suzuki R, Nishino S, Shimizu T
  • Organizer: the 28th Annual Meeting of the APSS
  • Place of Presentation: Minneapolis, MN
  • Year and Date: 2014-05-31 – 2014-06-04
• [Presentation] SYMPTOMATIC NARCOLEPSY AMONG INHERITED DISORDERS, SUCH AS NIEMANN-PICK TYPE C AND MYOTONIC DYSTROPHY TYPE 1 (2014)
  • Author(s): Imanishi A, Kanbayashi T, Shimohata T, Sagawa Y, Takahashi Y, Suda H, Takahashi J, Kubota H, Kikuchi Y, Shimizu T
  • Organizer: the 28th Annual Meeting of the APSS
  • Place of Presentation: Minneapolis, MN
  • Year and Date: 2014-05-31 – 2014-06-04
• [Presentation] DIFFERENTIATION OF CENTRAL AND OBSTRUCTIVE SLEEP APNEA BY FAST FOURIER TRANSFORM (FFT) ANALYSIS ON CARDIORESPIRATORY SIGNALS DETECTED BY A PIEZOELECTRIC SENSOR (2014)
  • Author(s): Sato S, Nishijima T, Kanbayashi T, Endou F, Tokunaga J, Sagawa Y, Sakurai S, Shimizu T, Nishino S
  • Organizer: the 28th Annual Meeting of the APSS
  • Place of Presentation: Minneapolis, MN
  • Year and Date: 2014-05-31 – 2014-06-04
• [Presentation] RESIDUAL EFFECTS OF ESZOPICLONE ON DAYTIME ALERTNESS, PSYCHOMOTOR AND PHYSICAL PERFORMANCE (2014)
  • Author(s): Suda H, Ito SU , Sagawa Y, Takahashi J, Kikuchi Y, Kanbayashi T, Shimizu T
  • Organizer: the 28th Annual Meeting of the APSS
  • Place of Presentation: Minneapolis, MN
  • Year and Date: 2014-05-31 – 2014-06-04
• [Presentation] ナルコレプシー診断におけるオレキシン測定の有用性 (2013)
  • Author(s): 佐川洋平 今西彩 武村尊生 林由理子 神林崇 清水徹男
  • Organizer: 日本睡眠学会 第38回定期学術集会
  • Place of Presentation: 秋田キャッスルホテル
• [Presentation] 発症前後のナルコレプシーモデルマウスにおける非侵襲的睡眠解析 (2013)
  • Author(s): 佐川洋平 有井潤子 佐藤紳一 西野精治
  • Organizer: 日本睡眠学会 第38回定期学術集会
  • Place of Presentation: 秋田キャッスルホテル
• [Presentation] ナルコレプシーマウスにおけるプロスタグランジンDP1受容体アンタゴニストONO-4127の覚醒促進効果 (2013)
  • Author(s): 佐川洋平 酒井紀彰 近久幸子 佐藤雅俊 千葉伸太郎 山本潤希 神林崇 清水徹男 西野精治
  • Organizer: 日本睡眠学会 第38回定期学術集会
  • Place of Presentation: 秋田キャッスルホテル
• [Presentation] 視神経脊髄炎(NMO)におけるオレキシン値の関連性の解析 (2013)
  • Author(s): 久保田弘樹 今西彩 矢野珠巨 佐川洋平 神林崇 高橋勉 清水徹男
  • Organizer: 日本睡眠学会 第38回定期学術集会
  • Place of Presentation: 秋田キャッスルホテル
• [Presentation] CSF QRFP CONCENTRATIONS IN NARCOLEPSY, NEUROLOGICAL AND PSYCHIATRIC DISORDERS (2013)
  • Author(s): Kanbayashi, T., Sagawa, Y., Imanishi, A., Takahashi, Y., Suda, H., Takahashi, J., Tokunaga, J., Sato, M., Sato, S., Shimizu
  • Organizer: The 27th Annual Meeting of the Associated Professional Sleep Societies
  • Place of Presentation: Baltimore, USA