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. 2014 Jul 15;23(24):6528–6541. doi: 10.1093/hmg/ddu371

Figure 8.

Figure 8.

OAA effects and inter-effect relationships. OAA, a bioenergetic intermediate, affects bioenergetic flux. This produces a number of molecular changes. CREB phosphorylation and CREB activity increase, which in turn promotes the expression of PGC1 family member genes. AMPK and p38 MAP phosphorylation increase, and these activated kinases enhance PGC1α co-activator function. PGC1-induced co-activation of the NRF1 transcription factor stimulates COX4I1 production, while PGC1-induced co-activation of the ERRα transcription factor stimulates VEGF gene expression (61). OAA-induced flux changes also stimulate the pro-growth insulin signaling pathway and reduce inflammation. The pro-growth effects of increased insulin pathway signaling and increased VEGF, in conjunction with a more favorable bioenergetic status and less inflammation, cooperatively stimulate hippocampal neurogenesis.