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 microM) 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.
Dagai
L
L
Ben Gurion University of the Negev, Beer-Sheva, Israel.
Peri-Naor
R
R
Birk
R Z
RZ
D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D051766:Early Growth Response Protein 1 / Q000096:biosynthesis; D051776:Early Growth Response Protein 3 / Q000096:biosynthesis; D017874:Immediate-Early Proteins / Q000096:biosynthesis*; D008565:Membrane Proteins / Q000096:biosynthesis; D020932:Nerve Growth Factor / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects* / Q000502:physiology; D016716:PC12 Cells; D051381:Rats; D013997:Time Factors; D025521:Tumor Suppressor Proteins
D000943:Antigens, Differentiation; C521959:BTG2 protein, rat; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; C497370:Egr3 protein, rat; C084979:Ifrd1 protein, rat; D017874:Immediate-Early Proteins; D008565:Membrane Proteins; D025521:Tumor Suppressor Proteins; D051776:Early Growth Response Protein 3; D004281:Docosahexaenoic Acids; D020932:Nerve Growth Factor
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