Docosahexaenoic acid significantly stimulates immediate early response genes and neurite outgrowth

Docosahexaenoic acid (22:6n - 3, DHA) is known to enhance neurogenesis. However, the immediate-early effect of DHA on neurogenesis is not fully elucidated. We studied the effect of DHA supplementation (10 and 30 μM) on morphological and molecular changes at different time points of nerve growth factor (NGF, 50 ng/ml)-induced differentiation of PC12 (pheochromocytoma) cells. Cells were analyzed throughout the differentiation process (2 h, 1, 2, 3, 4, and 10 days), for neurite outgrowth (light microscopy and computer image analysis), and for mRNA levels of the immediate molecular differentiation markers Egr1, Egr3, PC3 and PC4 (quantitative real-time PCR). DHA induced significant accelerated neurite outgrowth beginning as early as 2 h post-DHA supplementation and throughout differentiation. Transcripts of the neurogenesis immediate early biomarkers Egr3 and PC3 were significantly (P < 0.05) elevated following DHA supplementation within 0.5 and 1 h post-supplementation (respectively). In conclusion, we show that DHA significantly stimulates immediate-early neurogenesis events, as is evident by both morphological and molecular markers.