期刊
JOURNAL OF NEUROCHEMISTRY
卷 107, 期 6, 页码 1529-1543出版社
WILEY
DOI: 10.1111/j.1471-4159.2008.05718.x
关键词
dopamine glutamate neurotransmitters; ELAV; Hu; experience-dependent plasticity; fragile-X mental retardation protein; post-transcriptional regulation; RNA-binding proteins
资金
- National Institutes of Health [R33-CA94365]
Growing evidence indicates that both seizure (glutamate) and cocaine (dopamine) treatment modulate synaptic plasticity within the mesolimbic region of the CNS. Activation of glutamatergic neurons depends on the localized translation of neuronal mRNA products involved in modulating synaptic plasticity. In this study, we demonstrate the dendritic localization of HuR and HuD RNA-binding proteins (RBPs) and their association with neuronal mRNAs following these two paradigms of seizure and cocaine treatment. Both the ubiquitously expressed HuR and neuronal HuD RBPs were detected in different regions as well as within dendrites of the brain and in dissociated neurons. Quantitative analysis revealed an increase in HuR, HuD and p-glycogen synthase kinase 3 beta (GSK3 beta) protein levels as well as neuronal mRNAs encoding Homer, CaMKII alpha, vascular early response gene, GAP-43, neuritin, and neuroligin protein products following either seizure or cocaine treatment. Inhibition of the Akt/GSK3 beta signaling pathway by acute or chronic LiCl treatment revealed changes in HuR, HuD, pGSK3 beta, p-Akt, and beta-catenin protein levels. In addition, a genetically engineered hyperdopaminergic mouse model (dopamine transporter knockout) revealed decreased expression of HuR protein levels, but no significant change was observed in HuD or fragile-X mental retardation protein RBPs. Finally, our data suggest that HuR and HuD RBPs potentially interact directly with neuronal mRNAs important for differentiation and synaptic plasticity.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据