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

2014 Fiscal Year Final Research Report

• 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
• Keywords: Parkinson'd disease / sleep / AAV / Nucleus Accumbens / 6-OHDA / Striatum

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.

Free Research Field

neuroscience