Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Brain Res. 2010 Feb 22;1315:53-62. doi: 10.1016/j.brainres.2009.12.015. Epub 2009 Dec 21.
Chemokines are small secreted proteins that act as chemoattractants, and their role as neuromodulators in the brain has recently been appreciated. CXCL12 is one of the few chemokines found in neurons and expressed constitutively in the central nervous system. Previous data from our laboratory demonstrate the ability of CXCL12 to modulate the behavioral effects of cocaine, and this modulation is dependent on the central site of administration of CXCL12. The present study used single-staining immunohistochemical and dual-staining immunofluorescent methods to determine the localization of the CXCL12 receptor, CXCR4, in the caudate putamen and nucleus accumbens of the adult rat brain. Results demonstrated that individual neurons in both the caudate putamen and lateral shell of the nucleus accumbens express both CXCR4 and D1 dopamine receptors. Immunofluorescent studies showed that CXCR4 was co-expressed with ChAT, a marker for cholinergic neurons, and with GAD C38, a marker for GABAergic neurons, in the caudate putamen and lateral shell of the accumbens. No evidence of CXCR4 was found in the medial shell or core regions of the nucleus accumbens. These data demonstrate that CXCR4 is expressed by subpopulations of cholinergic and GABAergic neurons in the striatum and suggest that CXCR4 is well-positioned to modulate striatal function.
趋化因子是小的分泌蛋白,作为趋化因子起作用,最近人们认识到它们在大脑中作为神经调节剂的作用。CXCL12 是少数在神经元中发现并在中枢神经系统中持续表达的趋化因子之一。我们实验室的先前数据表明 CXCL12 能够调节可卡因的行为效应,这种调节依赖于 CXCL12 的中枢给药部位。本研究使用单染色免疫组织化学和双重染色免疫荧光方法来确定 CXCL12 受体 CXCR4 在成年大鼠脑的尾状核和伏隔核中的定位。结果表明,尾状核和伏隔核外侧壳中的单个神经元均表达 CXCR4 和 D1 多巴胺受体。免疫荧光研究表明,CXCR4 与 ChAT(胆碱能神经元的标志物)和 GAD C38(GABA 能神经元的标志物)在尾状核和伏隔核外侧壳中共表达。在伏隔核的内侧壳或核心区域未发现 CXCR4 的证据。这些数据表明 CXCR4 是纹状体中胆碱能和 GABA 能神经元的亚群表达的,表明 CXCR4 很好地定位于调节纹状体功能。