Project/Area Number |
16K19684
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Embryonic/Neonatal medicine
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Research Institution | Shiga University of Medical Science |
Principal Investigator |
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Project Period (FY) |
2016-04-01 – 2020-03-31
|
Project Status |
Completed (Fiscal Year 2019)
|
Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
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Keywords | 鉄欠乏 / 側坐核 / rat / Reelin / ラット / 鉄欠乏性貧血 / Reelin遺伝子 / 側座核 / 脳・神経 / 乳児栄養 / 解剖学 / 母体栄養 |
Outline of Final Research Achievements |
Fischer 344/Jcl postweaning male rats aged 21-39 d were fed low-iron diets (0.35 mg/kg iron; ID group) or standard AIN-93 G diets [3.5 mg/kg iron; control (CN) group]. Behavioral tests at 8 and 12 wk of age revealed a significant reduction of the age-related decline in the total distance traveled in ID rats compared with CN rats, indicating that ID affected hyperactivity, which persisted into adulthood (13 wk of age). At this age, reelin (Reln) mRNA expression decreased and synaptic density increased in the NAcc in the ID group. Regarding the mesolimbic pathway, homovanillic acid concentration increased in the NAcc,whereas the dopamine concentration decreased in the ventral midbrain. Our results suggest that ID during the postweaning period in male rats, despite complete iron repletion following ID, led to long-term hyperactivity via monoamine disturbance in the brain and an alteration in the synaptic plasticity accompanied by downregulation of Reln expression in the NAcc.
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Academic Significance and Societal Importance of the Research Achievements |
今回の実験で鉄制限を行った期間は、人間の9か月から2歳に相当し、現在の日本でも存在する離乳期の鉄欠乏性貧血のモデルラットと考えている。乳児期の鉄欠乏によりReelin遺伝子の発現量がエピジェネティックな変化により減少することで不可逆的な変化をもたらし、神経伝達物質やシナプス形成にも影響を与え、成人期にも行動特性が残る一因となることを明らかにしたのではないかと考えている。今後は乳児期の鉄欠乏を予防することで、不可逆的な変化と思われる成人期の行動特性を予防することにつながるのではないかとと考えている。
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