罗格列酮对海马神经元树突发育的影响

罗格列酮(rosiglitazone，Rosig.)是噻唑烷二酮类(thiazolidinediones，TZDs)过氧化物酶体增殖物激活受体γ(peroxisome proliferator-activated receptor gamma，PPARγ)的激动剂，近年来，临床研究发现其具有神经保护作用，但对其作用机制目前仍没有完全研究清楚．利用活细胞成像的方法，观察罗格列酮对大鼠海马神经元树突丝和树突树发育的影响及其机制．结果显示，罗格列酮浓度依赖的增高神经元树突丝密度，对树突丝长度、运动速度并没有影响．此外，罗格列酮也不影响树突树的总分支、总长度以及各级分支的数目和长度．PPARγ 特异性拮抗剂GW9662完全阻断了罗格列酮介导的树突丝密度增高．结果表明罗格列酮可能通过PPARγ途径影响神经元的早期发育，这可能是罗格列酮发挥神经保护作用的潜在机制．

The Effect of Rosiglitazone on The Dendritic Development of Hippocampal Neurons

Rosiglitazone,a PPARγ 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 μmol/L) or 20 μmol/L rosiglitazone with the presence of 5 μmol/L GW9662,an antagonist of PPARγ,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 μmol/L((34.27 ± 2.12)/100 μm,n = 21) and 20 μmol/L((37.75 ± 2.09)/100 μm,n=21) rosiglitazone treated group was significantly increased compared with those of control group((26.45±1.47)/100 μm,n=21),but the filopodia density of cultured neurons in 5 μmol/L rosiglitazone treated group((27.66 ± 1.84)/100 μm,n=20) was not significantly altered compared with those of control group.Rosiglitazone treatment of 5,10 and 20 μmol/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 μmol/L rosiglitazone.5 μmol/L GW9662 attenuated the increased filopodia density induced by 20 μmol/L rosiglitazone.These results suggest that rosiglitazone may affect the initial stage of hippocampal neuron development through the PPARγ pathway.This may be a possible mechanism of the neuroprotective effects of rosiglitazone.