PPARγ Activation TGZ Promotes Axon Elongation By A Mechanism That Involved JNK Activation

The hippocampus is important functional areas of the central nervoussystem, and learning, memory and other physiological functions are closelylinked with it, and many neurodegenerative diseases such as Alzheimer’sdisease (AD), Parkinson’s disease (PD), Huntington’s disease (HD),amyotrophic lateral sclerosis (ALS) are all related to the site of the lesion[1、2].Early studies suggest that the age-related cognitive decline and the loss ofneurons may be related, but more and more evidence proved that in the normalaging process, the number of neurons has not changed significantly, and theshortening of axis which led to synaptic dysfunction and neuronal cell deathmay be the basic pathological features of neurodegenerative diseases[3、4].Peroxisome proliferator-activated receptors (PPARs) play an importantrole in the gene transcription. The current study shows that, PPARs can protectnerve cells, and have potential applications in the treatment ofneurodegenerative diseases[5]. PPARs include PPARα, PPARβ, PPARγ threesubtypes. With an important role in treating metabolic diseases, PPARγbecome a hot topic.And only binding to the corresponding ligand, PPARγ canplay a physiological effect. As a PPARγ potent activator, troglitazone (TGZ) isused in the clinical treatment of diabetes, but the application in diseases of thenervous system is still relatively little[6]. It was founded that after treatmentwith PPARγ agonists on pheochromocytoma cells (PC12), we couldsignificantly promote the extension of its synapses, and this role in promotingwas associated with the activation of MAPK-JNK pathway, but whetherPPARγ pathway impact axon growth has not been reported[7].In this research, we select hippocampal neurons, the most representativetype of neurons, as the research object. Through treatment of PPARγ agonistand antagonist, we will explore the role of PPARγ in extending of hippocampal neurons axons and mechanism of the process.Purpose:TGZ, PPARγ activators, can promote the growth of axons in hippocampalneurons, the mechanism is TGZ will activate JNK pathway in promoting axon.Method:First, Isolate the endogenous mouse embryonic hippocampal neurons,andthe purity is more than90%.Second, by western blot we proved that TGZ andGW9662will regulate the expression of PPARγ and activation of theJNK.Third, after treatments of TGZ, GW9662, SP600125on different groupsof cells, we measure the cell axon by immunofluorescence stainingquantitative cell analysis.Results:The purity of hippocampal neurons cultured is proved to be more than90%by anti-tau staining; western blot results prove TGZ and GW9662caneffectively regulate the expression levels of PPARγ protein（P<0.05）, and TGZand GW9662can promote phosphorylation of JNK protein（P<0.05）; TGZ canpromote axon extension （P<0.05）, and the most significant effect is72h,GW9662can inhibit neurite promoting effect of TGZ, GW9662do not affectneurite growth of normal cells（P>0.05）, which proves that TGZ can activatePPARγ protein effectively. After the application of JNK pathway inhibitorSP600125, the role of TGZ on promoting axon has been inhibited (P <0.05),which proves the effect of promoting axon is based on the activation of JNKpathway.Conclusion:TGZ can promote hippocampal neurons extend axons, this effect isachieved through the activation of PPARγ, but the mechanism of this effect ismediated by the JNK pathway.