The Effect of Rosiglitazone on The Dendritic Development of Hippocampal Neurons

Rosiglitazone, a PPAR gamma thiazolidinediones (TZDs) agonist, has been proposed to have neuroprotective effects in the central nervous system (CNS). However, the mechanisms underlying the beneficial effects of rosiglitazone are unclear. In the present study, primary cultured hippocampal neurons of 1-day-old wistar rats were transfected with farnesylated enhanced green fluorescent protein (F-GFP) and GFP-actin on day 5 in vitro (DIV5) to display the morphological details of the dendrites and dendritic protrusions. Different doses of rosiglitazone (5, 10 and 20 mu mol/L) or 20 mu mol/L rosiglitazone with the presence of 5 mu mol/L GW9662, an antagonist of PPAR gamma, were applied to neurons for 24 h at DIV6. Live-cell imaging technology was used to investigate the effects of rosiglitazone on the development of dendritic filopodia and dendritic tree in hippocampal neurons at DIV7. Our results have shown that rosiglitazone increased the density of dendritic filopodia in a dose-dependent manner. The filopodia density of cultured neurons in 10 mu mol/L ((34.27 +/- 2.12)/100 mu m, n = 21) and 20 mu mol/L ((37.75 +/- 2.09)7100 mu m, n=21) rosiglitazone treated group was significantly increased compared with those of control group((26.45 +/- 1.47)/100 mu m, n=21), but the filopodia density of cultured neurons in 5 mu mol/L. rosiglitazone treated group ((27.66 +/- 1.84)/100 mu m, n=20) was not significantly altered compared with those of control group. Rosiglitazone treatment of 5, 10 and 20 mu mol/L concentrations has no effect on the length and motility of dendritic filopodia. In addition, neither the length nor the number of dendritic branches was altered by treatment of 5, 10 and 20 mu mol/L rosiglitazone. 5 mu mol/L GW9662 attenuated the increased filopodia density induced by 20 mu mol/L rosiglitazone. These results suggest that rosiglitazone may affect the initial stage of hippocampal neuron development through the PPAR gamma pathway. This may be a possible mechanism of the neuroprotective effects of rosiglitazone.