Background: 

PPARs are a subfamily of the nuclear hormone receptor that heterodimerizes with the retinoid X receptor to act as a transcriptional regulator. Recently it has been shown that the activation of PPARg isoform promotes neuronal differentiation.

Aim: 

In this study we have investigated the capability of synthetic compounds endowed with different activity profile on PPARa/g subtypes to induce neuronal differentiation and neurite outgrowth. The experiments were carried out on cells of the human neuroblastoma SH-SY5Y line. Retinoic acid (RA) was used as a positive control for neurite outgrowth.

Methods: 

SH-SY5Y cultures were maintained in DMEM supplemented with 10% FCS. 10mM RA, 0,5 to 25mM PPAR agonist was added to the culture media in the experimental cultures. Cell viability was tested using the MTT assay. Changes in the expression and re-organization of specific markers involved in neuronal differentiation were investigated using immunofluorescence.

Results: 

Synthetic PPAR agonists promote cell differentiation and the outgrowth of cell processes in a concentration-dependent manner. The maximal effect was obtained at a concentration of 25mM. At this concentration we obtained a significant increase of the expression of neurofilament-200 (NF-H) and Gap-43; this agrees with a hypothesis of cell differentiation induced by these molecules.

Conclusion: 

Our results suggest that sintetic PPAR agonist promotes neuronal differentiation and neurite outgrowth in SH-SY5Y human neuroblastoma cells. Further work on this subject is underway in our laboratories.