2014 Fiscal Year Annual Research Report
Implication of the striatopallidal pathway in Parkinson's disease related sleep disorder
| Project/Area Number |
25871082
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| Research Institution | University of Tsukuba |
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Principal Investigator |
シェラス ヨアン 筑波大学, 国際統合睡眠医科学研究機構, 研究員 (60544319)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Keywords | 6-OHDA / Dorsal striatum / SNc / Parkinson disease / AAV / sleep |
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| Outline of Annual Research Achievements |
Adeno-associated virus (AAV) expressing the neuron activating “designer receptors exclusively activated by a designer drug” (DREADDs) hM3Dq have been bilaterally injected into the nucleus accumbens (NAc) of Adora2a-Cre mice with 6-OHDA (4ug diluted into 1uL of artificial CSF) to generate a mouse model of Parkinson’s disease (PD) in which Adora2a positive neurons can be activated.
After implantation of sleep recording apparatus, we recorded sleep in these animals. In wild type animals, 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 after saline or CNO injections (0.1, 0.3 or 1mg/kg). We may hypothesize that the dopaminergic activation of NAc neurons is important for the sleep inducing effect observed after the activation of A2aR neurons in NAc.
Furthermore, we tested the memory ability by performing the New Object Recognition (NOR) test on the same mouse model after A2aR positive neurons activation by CNO injection. Compared to saline, CNO injection improved mice ability to recognize previous object: number of activation was reduced by 33.3% (versus 23.1% for saline), time spent near the object was reduced by 44.1% (versus 25.3% for saline) and the latency to the 1st activation was increased by 205% (versus 19% for saline).
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