| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
Docosahexaaenoic acid (DHA), one of the main structural lipids in the mammalian brain, plays crucial roles in the development and function of brain neurons. We previously reported that chronic administration of DHA enhances long-term memory in young and aged rats, and dietary DHA has preventive and ameliorative effects on the impairment of spatial cognition learning ability in amyloid b-infused rats. These findings suggest that DHA plays crucial roles in the development and function of the CNS throughout life. In this study, we examined the 1) effect of DHA on neural differentiation of neural stem cells (NSCs) in vivo and in vitro, and 2) on the expression of basic helix-loop-helix (bHLH) transcriptional factors of the cultured cells.
<Methods> NSCs obtained from 15.5-day-old rat embryos were propagated as neurospheres and cultured under differential conditions with or without DHA. Total RNA was prepared from each culture with or without DHA, and was performed RT-PCR (Hes1, Hes5, neurog
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enin1, Mash1 or NeuroD).
<Results and Conclusions> 1) DHA significantly increased the number of Tuj 1-positive neurons compared with the control on cultured NSCs, and the newborn neurons in the DHA groups were morphologically more mature than in the control, DHA significantly decreased the incorporation ratio of 5-bromo-2-deoxyuridine, the mitotic division marker, during the first 24h periods. Furthermore, dietary administration of DHA significantly increased the number of 5-bromo-2-deoxyuridine(+)/NeuN(+) newborn neurons in the granule cell layer of the dentate gyrus in adult rats. These results suggested that DHA effectively promotes nuerogenesis both in vitro and in vivo.
2) Treatment of NSCs with DHA decreased the expression of Hes1 mRNA compared with that of control, suggesting that DHA stimulates neuronal differentiation by modulating expression levels of bHLH transcription factors.
The present study suggests that DHA has the new property of modulating hippocampal function regulated by neurogenesis. Less
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