| Project/Area Number |
17H06563
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurophysiology / General neuroscience
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| Research Institution | Keio University |
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Principal Investigator |
Ishii Seiji 慶應義塾大学, 医学部(信濃町), 特任講師 (50468493)
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| Project Period (FY) |
2017-08-25 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 大脳皮質 / 樹状突起 / 環境ストレス応答 / アルコール曝露 / 環境ストレス / アルコール / ゴルジ体 / アルコール投与 |
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| Outline of Final Research Achievements |
To test the roles of cilia in brain development under exposure to environmental insults, we utilized a conditional knockout (cKO) of intraflagellar transport 88 (Ift88). Ift88 floxed mice were crossed with mice carrying the transgene Emx1-IRES-Cre (Emx1-Cre) by which Cre is expressed specifically in the dorsal pallium-originated cortical cells. The number of activated caspase-3-positive neurons remained small 24 hours post exposure in conditional heterozygote (cHet) control mice, while the number was significantly larger in cKO mice. We next found that dendritic complexity was significantly decreased; Thy1-YFP-labeled layer V neurons in EtOH-exposed cKO mice exhibited fewer dendrites with fewer and shorter branches than those in other groups. These results suggest that there might be the primary cilia-dependent neuroprotective function activated by environmental stress.
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| Academic Significance and Societal Importance of the Research Achievements |
一次繊毛の形成、機能異常に起因すると考えられている遺伝性疾患は総称して繊毛病（シリオパチー）と呼ばれ、網膜色素変性症、嚢胞腎、多指症、水頭症、不妊、肥満など、多岐にわたる症状を呈することが知られている。本研究において「環境ストレスに対する一次繊毛を介した臨界期中枢神経系の防御機構」の分子基盤を明らかにする事で、ストレス応答という新たな視点から一次繊毛に対する理解が深まるものと期待される。本研究において得られた知見は、今後、多岐にわたる繊毛病の発症メカニズムの理解や新たな治療法への応用に貢献できるものと考えられる。
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