Role of retinoids in the CNS:: differential expression of retinoid binding proteins and receptors and evidence for presence of retinoic acid
Role of retinoids in the CNS:: differential expression of retinoid binding proteins and receptors and evidence for presence of retinoic acid
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DOI：
10.1046/j.1460-9568.1999.00444.x
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发表时间：
1999-02-01
影响因子：
3.4
通讯作者：
Olson, L
中科院分区：
文献类型：
--
作者：
Zetterström, RH;Lindqvist, E;Olson, L
视黄酸（RA）是一种类维甲酸代谢物，通过配体激活的转录因子，即视黄酸受体（RARs）和类视黄酸X受体（RXRs），作为基因调节剂，存在于α、β和γ三种不同的亚型中。在类维甲酸的细胞内调控中，涉及四种结合蛋白：细胞视黄醇结合蛋白（CRBP） I型和II型和细胞维甲酸结合蛋白（CRABP） I型和II型。我们使用原位杂交定位编码CRBP-和CRABP I和II以及发育和成年大鼠和小鼠中枢神经系统（CNS）中所有不同核受体的mRNA物种，研究RA可能存在的分析，以及免疫组织化学分析CRBP-和CRABP I的免疫反应性（IR）。RXR β出现在大多数区域，而RAR α和- β以及RXR α和- γ的表达模式更为有限。RAR α在皮层和海马中发现，RAR β和RXR γ在多巴胺支配的尾状核/壳核、伏隔核和嗅结节中都有高表达。中枢神经系统的任何部位都检测不到RAR。使用体外报告试验，我们在发育中的纹状体中发现了高水平的类风湿性关节炎。发育中的脑尾状核/壳核显示出较强的CRBP I-IR，且呈区隔性分布，同时含有许多均匀分布的CRBP I-IR神经元。CRBP I-和CRABP I- ir模式由于相应转录本的存在而密切平行。类视黄酮结合蛋白和核类视黄酮受体的特异性表达模式以及类视黄酮在纹状体中的存在表明类视黄酮在许多脑结构中都很重要，并强调了类视黄酮在出生后和成年纹状体中基因调控事件中的作用。
Retinoic acid (RA), a retinoid metabolite, acts as a gene regulator via ligand-activated transcription factors, known as retinoic acid receptors (RARs) and retinoid X receptors (RXRs), both existing in three different subtypes, alpha, beta and gamma. In the intracellular regulation of retinoids, four binding proteins have been implicated: cellular retinol binding protein (CRBP) types I and II and cellular retinoic acid binding protein (CRABP) types I and II. We have used in situ hybridization to localize mRNA species encoding CRBP- and CRABP I and II as well as all the different nuclear receptors in the developing and adult rat and mouse central nervous system (CNS), an assay to investigate the possible presence of RA, and immunohistochemistry to also analyse CRBP I- and CRABP I immunoreactivity (IR). RXR beta is found in most areas while RAR alpha and -beta and RXR alpha and -gamma show much more restricted patterns of expression. RAR alpha is found in cortex and hippocampus and RAR beta and RXR gamma are both highly expressed in the dopamine-innervated areas caudate/putamen, nucleus accumbens and olfactory tubercle. RAR gamma could not be detected in any part of the CNS. Using an in vitro reporter assay, we found high levels of RA in the developing striatum. The caudate/putamen of the developing brain showed strong CRBP I-IR in a compartmentalized manner, while at the same time containing many evenly distributed CRABP I-IR neurons. The CRBP I- and CRABP I-IR patterns were closely paralleled by the presence of the corresponding transcripts. The specific expression pattern of retinoid-binding proteins and nuclear retinoid receptors as well as the presence of RA in striatum suggests that retinoids are important in many brain structures and emphasizes a role for retinoids in gene regulatory events in postnatal and adult striatum.