Activator-type bHLH transcription factors such as Hes6, neurogenin, Mash1, and NeuroD enhanced the expression of MAP2, a neuron specific protein, and induced neuronal differentiation.
Hes6, an inhibitor of Hes1, was also significantly increased by EPA treatment on day 1, but not on day 4 (Figure 3(b)).
It was observed that EPA treatment induced neuronal differentiation in cultured NSCs and increased mRNA levels of Hes1, an inhibitory factor of neuronal differentiation, and Hes6, an inhibitory factor of Hes1.
In the present study, EPA increased Hes1 mRNA expression, Map2 mRNA expressions and the number of Tuj-1-positive cells because Hes6 acts in a positive feedback loop in neurogenesis by competing with Hes1 activation and promoting proteolytic degradation of Hes1 [23,24].
Hes6 expression appears to activate [p21.sup.cip1] transcription, suppresses cell proliferation [28], and may also affect the cell cycle.
DHA decreased Hes1 expression levels and EPA increased Hes6 expression levels, which led to a decreased Hes1 activity.
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