Cis-9,trans-11-conjugated linoleic acid promotes neuronal differentiation through regulation of Hes6 mRNA and cell cycle in cultured neural stem cells

Conjugated linoleic acids (CLAs) are positional and geometrical isomers of linoleic acid (LA). Cis-9,trans-11-CLA (CLA), the main isomer of CLAs in foods derived from ruminants, has several beneficial effects for humans and animals; however, its effects on the central nervous system are largely unknown. In this study, we investigated the effects of LA and CLA on neuronal differentiation of neural stem cells (NSCs). NSCs cultured with or without LA and CLA were assessed by immunofluorescence staining, mRNA measurement of basic helix-loop-helix transcription factors and cyclin-dependent kinase inhibitors by real-time PCR, BrdU incorporation analysis and flow cytometry analysis. In NSCs treated with CLA, the number of Tuj-1-positive cells (neurons) and the mRNA expression levels of Hes6, MAP2, p21cip1 and p27kip1 increased, while the proportion of S-phase cells decreased; compared with the control, no change was demonstrated in NSCs treated with LA. These results suggest that CLA promotes neuronal differentiation by increasing, in part, the expression of Hes6 mRNA and by activating p21cip1 and p27kip1 to arrest cell cycle.

► CLA induces neuronal differentiation of neural stem cells.
► CLA increases Hes6, Mash1 and MAP2 mRNA levels in neural stem cells.
► CLA arrests G1- to S-phase in cell cycle by inducing p21 and p27 mRNA levels.