Micro RNA-124 slows down the progression of Huntington's disease by promoting neurogenesis in the striatum

MicroRNA-124 contributes to neurogenesis through regulating its targets, but its expression both in the brain of Huntington＇s disease mouse models and patients is decreased. However, the effects of microRNA-124 on the progression of Huntington＇s disease have not been reported. Results from this study showed that microRNA-124 increased the latency to fall for each R6/2 Hunting- ton＇s disease transgenic mouse in the rotarod test. 5-Bromo-2＇-deoxyuridine （BrdU） staining of the striatum shows an increase in neurogenesis. In addition, brain-derived neurotrophic factor and peroxisome proliferator-activated receptor gamma coactivator 1-alpha protein levels in the striatum were increased and SRY-related HMG box transcription factor 9 protein level was de- creased. These findings suggest that microRNA-124 slows down the progression of Huntington＇s disease possibly through its important role in neuronal differentiation and survival.

Flurbiprofen axetil promotes neuroprotection by activation of cerebral peroxisome proliferator-activated receptor gamma after focal cerebral ischemia in rats

Background Our previous papers indicate that flurbiprofen axetil （FA）, a cyclooxygenase inhibitor, is a promising therapeutic strategy for cerebral ischemia in rats. This study aimed to investigate whether FA could promote a neuroprotective effect by activation of peroxisome proliferator-activated receptor-y （PPAR-y） after focal cerebral ischemia in rats. Methods Totally 48 male Sprague-Dawley （SD） rats were randomly assigned into six groups （n=8 in each group）： animals in group ischemia/reperfusion （I/R） only received 120-minute transient middle cerebral artery occlusion （tMCAO）; animals in group I/R ＋FA were administered FA （10 mg/kg） by caudal vein just after 120-minute tMCAO; animals in group I/R ＋FA＋GW9662 were administered GW9662 （a PPAR-Y inhibitor, 1 mg/kg） intraperitoneally 30 minutes before cerebral ischemia onset and FA （10 mg/kg） by caudal vein just after 120-minute tMCAO; animals in group I/R ＋GW9662 were administered GW9662 （1 mg/kg） intraperitoneally 30 minutes before cerebral ischemia onset; animals in group I/R ＋DMSO were administered 3% DMSO （vehicle of GW9662, 1 ml/kg） intraperitoneally 30 minutes before cerebral ischemia onset; animals in sham group experienced the identical surgery apart from the insertion of the nylon filament. The neurologic deficit score （NDS） were performed at 72 hours after reperfusion, and then mean brain infarct volume percentage （MBIVP） was determined with 2,3,5-triphenyltetrazolium chloride （TTC） 10 g/L staining. Results NDS was significantly increased in group I/R＋FA （12.0 （10.0-15.0））, group I/R＋FA＋GW9662 （10.0 （8.0-12.0））, and in group I/R＋FA＋DMSO （12.0 （9.0-14.0）） at 72 hours after reperfusion compared with those in group I/R （7.5 （6.0-10.0））. NDS was conspicuously different between group I/R＋FA （12.0 （10.0-15.0）） and group I/R＋FA＋GW9662 （10.0 （8.0-12.0））. MBIVP in group I/R （（45.82±8.83）%） was significantly greater than that in group I/R＋FA （（23.52±9.90）%）, group I/R＋FA＋GW9662 （（33.17±7.15）%）; MBIVP in group I/R＋FA （（23.52±9.90）%） was significantly smaller than that in group I/R＋FA＋GW9662 （（33.17±7.15）%）. Conclusions FA confers the neuroprotective effect on tMCAO in rats and the selective PPAR-Y antagonist GW9662 attenuates the effect of FA. FA could promote a neuroprotective effect by, or in part, activation of PPAR-y after focal cerebral ischemia in rats.

Peroxisome proliferator-activated receptor a agonist attenuates oxidized-low density lipoprotein induced immune maturation of human monocyte-derived dendritic cells

Accumulating evidence suggests that the Thl immune .response induced by various antigens such as oxidized low density lipoprotein （ox-LDL） and heat shock proteins （HSPs） play a key role in the process of atherosclerosis.1Dendritic cells （DCs） are the most potent antigen-presenting cells （APCs） in the body with the unique ability to initiate a primary immune response to certain antigens by the activation of ＂naive＂ T cells.2 The maturation of DC with the upregulation of costimulatory molecules such as CD83, CD40, CD86, and major histocompatibility complex （MHC） class molecules such as human leukocyte antigen （HLA）-DR, is required for DC to activate T cells. Pathologic studies have shown that immature DCs are present in normal arterial while abundant mature DCs clustered with T cells could be visualized in atherogenic vessels suggesting that DC 3 maturation is linked to the progression of atherosclerosls. Peroxisome proliferator-activated receptors （PPARs） a, one member of the family of PPARs, was found to have favorable effects on slowing the progression of atherosclerosis and reducing the risk of coronary heart disease in high-risk patients independent from their metabolism effects.4＇5 Furthermore, PPAR-α is also expressed on monocytes and monocyte-derived DCs.6 The effects of PPAR-α on DCs maturation and immune function remain unknown now, we therefore observed the effects of fenofibrate, a PPAR-α agonist, on the maturation and immune function of oxidized LDL-treated DCs in this study.