Implication of the striatopallidal pathway in Parkinson's disease related sleep disorder

• Project/Area Number: 25871082
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Nerve anatomy/Neuropathology; Neurochemistry/Neuropharmacology
• Research Institution: University of Tsukuba
• Principal Investigator: CHERASSE Yoan 筑波大学, 国際統合睡眠医科学研究機構, 研究員 (60544319)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: Parkinson'd disease / sleep / AAV / Nucleus Accumbens / 6-OHDA / Striatum / Dorsal striatum / SNc / Parkinson disease

Outline of Final Research Achievements

To annihilate dopaminergic neurons projecting into the dorsal striatum, we stereotaxically micro-injected 6-OHDA into the Nucleus Accumbens (NAc) or the Substancia Nigra pars compacta of C57BL/6 mice. We recorded sleep and observed a dramatic reduction of sleep compared to control mice. This effect is particularly severe during dark phase.
AAV-DREADD-hM3Dq have been injected into the NAc of Adora2a-Cre mice with 6-OHDA to generate a mouse model of Parkinson’s disease (PD) in which Adora2a positive neurons can be activated. In control animals (no 6-OHDA), activation of the Adora2a positive neurons in the NAc leads to an increase of NREM sleep. However, after the elimination of the dopaminergic activation of the NAc Adora2a positive neurons we could not observe anymore such phenotype and the total amount of sleep remained unchanged. Furthermore, CNO injection improved mice ability to recognize previous object in the New Object Recognition test.

Research Products

• [Journal Article] Projections of nucleus accumbens adenosine A2A receptor neurons in the mouse brain and their implications in mediating sleep-wake regulation (2013)
  • Author(s): Zhang J, Xu Q, Yuan X, Cherasse Y, Schiffmann SN, De Kerchove D'Exaerde A, Qu W, Urade Y, Lazarus M, Huang ZL, Li R
  • Journal Title: Frontiers in neuroanatomy Volume: 7 Pages: 1-15
  • DOI: 10.3389/fnana.2013.00043
  • NAID: 120007130584
  • Peer Reviewed
• [Presentation] Implication Of The Striatopallidal Pathway In Parkinson's Disease (Pd) Related Sleep Disorder (2015)
  • Author(s): Yoan Cherasse, Bin-Jia Zhang, Yoshihiro Urade, Michael Lazarus
  • Organizer: World Association of Sleep Medicine WASM2014
  • Place of Presentation: COEX Seoul, South Korea
  • Year and Date: 2015-03-21 – 2015-03-25
• [Presentation] Zinc induces NREM sleep in mice (2014)
  • Author(s): Yoan Cherasse
  • Organizer: Updated Progress on Sleep and Respiratory Diseases
  • Place of Presentation: Shanghai, China
  • Year and Date: 2014-10-31 – 2014-11-03
  • Invited
• [Presentation] Implication of the striatopallidal pathway in Parkinson's disease related sleep disorder (2014)
  • Author(s): Yoan Cherasse, Bin-Jia Zhang, Yoshihiro Urade, Michael Lazarus
  • Organizer: 日本睡眠学会第39 回定期学術集会
  • Place of Presentation: ホテルクレメント徳島(徳島徳島市)
  • Year and Date: 2014-07-03 – 2014-07-04
• [Remarks] WPI-IIIS Urade laboratory
  • URL: http://urade.wpi-iiis.tsukuba.ac.jp/
• [Remarks] WPI-IIIS Lazarus Laboratory
  • URL: http://www.wpiiiislazaruslab.org/