|Budget Amount *help
¥141,570,000 (Direct Cost: ¥108,900,000、Indirect Cost: ¥32,670,000)
Fiscal Year 2020: ¥22,750,000 (Direct Cost: ¥17,500,000、Indirect Cost: ¥5,250,000)
Fiscal Year 2019: ¥22,750,000 (Direct Cost: ¥17,500,000、Indirect Cost: ¥5,250,000)
Fiscal Year 2018: ¥23,660,000 (Direct Cost: ¥18,200,000、Indirect Cost: ¥5,460,000)
Fiscal Year 2017: ¥23,660,000 (Direct Cost: ¥18,200,000、Indirect Cost: ¥5,460,000)
Fiscal Year 2016: ¥48,750,000 (Direct Cost: ¥37,500,000、Indirect Cost: ¥11,250,000)
|Outline of Final Research Achievements
It is important to consider the concept of epigenetics for development of the individuality. By focusing on the property of neural stem/progenitor cells (NS/PCs) residing in the adult hippocampus, we identified the mechanism of increased seizure sensitivity in prenatally HDAC inhibitor VPA-exposed adult mice. Furthermore, we found that voluntary exercise can overcome the adverse effects through normalizing VPA-induced transcriptome alterations in NS/PCs.
We also elucidated the mechanism whereby a transcription factor NeuroD1 converts microglia into induced neuronal (iN) cells accompanied by global remodeling of microglial epigenetic signature. Furthermore, iN cells were functionally integrated into brain circuits through synaptic connections with other neurons like endogenous neurons. These findings bring us one step closer to developing therapeutic strategies for nerve injury and disease by reprogramming microglia that accumulate at lesion sites into neurons.