Woods John W, Tanen Michael, Figueroa David J, Biswas Chhabi, Zycband Emanuel, Moller David E, Austin Christopher P, Berger Joel P
Department of Inflammation Research, Merck Research Laboratories, Box 2000, RY80N-A43, 126 East Lincoln Avenue, Rahway, NJ 07065 USA.
Brain Res. 2003 Jun 13;975(1-2):10-21. doi: 10.1016/s0006-8993(03)02515-0.
The peroxisome proliferator-activated receptors (PPARs), PPARdelta, PPARgamma and PPARalpha, comprise a subclass of the supergene family of nuclear receptors. As such they are ligand-regulated transcription factors whose major effects are mediated by altering expression of target genes. PPARdelta has been shown to be ubiquitously expressed in mammals. However, its primary biological role(s) has yet to be defined. Several recent studies have demonstrated that PPARdelta is the most highly expressed PPAR isoform in the central nervous system, but ambiguity still exists as to the specific brain sub-regions and cells in which it is expressed. Here, utilizing novel, isoform-selective PPARdelta riboprobes and an anti-peptide antibody, we performed a series of in situ hybridization and immunolocalization studies to determine the distribution of PPARdelta in the central nervous system (CNS) of mice. We found that PPARdelta mRNA and protein is expressed throughout the brain, with particularly high levels in the entorhinal cortex, hypothalamus and hippocampus, and lower levels in the corpus callosum and caudate putamen. At the cellular level, PPARdelta mRNA and protein were found to be expressed in oligodendrocytes and neurons but not astrocytes. Such results suggest a role for PPARdelta in both myelination and neuronal functioning within the CNS.
过氧化物酶体增殖物激活受体（PPARs），即PPARδ、PPARγ和PPARα，属于核受体超基因家族的一个亚类。因此，它们是配体调节的转录因子，其主要作用是通过改变靶基因的表达来介导的。PPARδ已被证明在哺乳动物中普遍表达。然而，其主要生物学作用尚未明确。最近的几项研究表明，PPARδ是中枢神经系统中表达最高的PPAR亚型，但它在哪些特定的脑亚区域和细胞中表达仍不明确。在这里，我们利用新型的、亚型选择性的PPARδ核糖探针和抗肽抗体，进行了一系列原位杂交和免疫定位研究，以确定PPARδ在小鼠中枢神经系统（CNS）中的分布。我们发现，PPARδ mRNA和蛋白在整个大脑中都有表达，在内嗅皮质、下丘脑和海马中水平特别高，在胼胝体和尾状壳核中水平较低。在细胞水平上，发现PPARδ mRNA和蛋白在少突胶质细胞和神经元中表达，但在星形胶质细胞中不表达。这些结果表明PPARδ在中枢神经系统的髓鞘形成和神经元功能中都发挥作用。
