| Project/Area Number |
17H06978
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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 |
Orthodontics/Pediatric dentistry
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| Research Institution | Kagoshima University |
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Principal Investigator |
Furukawa Minami 鹿児島大学, 医歯学域附属病院, 助教 (00806474)
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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 | 幼少期ストレス / GABAスイッチ / KCC2 / NKCC1 / シナプス / 筋異常疼痛 / 薬理遺伝学 |
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| Outline of Final Research Achievements |
In recent years, it is reported early life stress is involved in the onset of psychiatric disorders, developmental disorders, muscle pain. However, the cause is unknown. We examined whether neonatal stress can affect the timing of the GABA functional switch and cause disorders during adolescence. Neonatal stress was induced in C57BL/6J male mouse pups by maternal separation on postnatal days (PND) 1-21. We showed that maternal separation delayed the timing of the GABA switch in the hippocampus and inhibited the increase in membrane KCC2 expression, with KCC2 expression inhibition persisting until adolescence. Behavioral tests showed impaired cognition, declined attention, hyperlocomotion, and aggressive character in maternally separated mice. Taken together, our results show that neonatal stress delayed the timing of the GABA switch, which could change the E/I balance and cause neurodegenerative disorders in later life.
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| Academic Significance and Societal Importance of the Research Achievements |
幼少期ストレスが、精神疾患や発達性障害、筋異常疼痛などの発症に関与することが報告されている。我々は幼少期ストレスにより、GABAスイッチが遅れ、細胞体周囲のKCC2の発現が減少し、NKCC1はほとんど影響を受けないことを初めて報告した。これにより、KCC2やGABAスイッチを介した、精神疾患や発達性障害、筋異常疼痛などの発症の予防、改善に抑制系の成熟を標的とした新たな治療法の確立が期待される。
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