2019 Fiscal Year Annual Research Report
Identification the signaling pathway of a novel sleep regulatory molecule SIK3 protein kinase
| Project/Area Number |
17K15592
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| Research Institution | University of Tsukuba |
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Principal Investigator |
Ma Jing 筑波大学, 国際統合睡眠医科学研究機構, 研究員 (70793222)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | sleep / SNIPPs / single prolonged stress / mPFC / PTSD |
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| Outline of Annual Research Achievements |
In the research period, we have investigate the function of several SNIPPs through pharmacological and AAV overexpression approaches; conditional knockout mice and specific phosphorylation site knock-in mice for SNIPPs genes have been generated to elucidate their roles in sleep regulation and function. These projects will be completed in next several years.
In addition, we performed a research on post-traumatic stress disorders (PTSD). Sleep disturbances have been recognized as a core symptom of PTSD. However, the neural basis of PTSD-related sleep disturbances remains unclear. It has been challenging to establish the causality link between a specific brain region and traumatic stress-induced sleep abnormality. Here, we found that single prolonged stress (SPS) could induce acute changes in sleep/wake duration as well as short and long-term electroencephalogram (EEG) alterations in the isogenic mouse model. Moreover, the medial prefrontal cortex (mPFC) showed persistent hyper-activity during and immediately after SPS. Chemogenetic inhibition of the prelimbic region of mPFC during SPS could specifically reverse the SPS-induced acute suppression of delta power (1-4Hz EEG) of non-rapid-eye-movement sleep (NREMS) as well as long-term EEG abnormalities. These findings suggest a causality link between hyper-activation of mPFC neurons and traumatic stress-induced sleep-wake EEG disturbances.
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