Gonçalves Isabel, Hubbard Peter C, Tomás Joana, Quintela Telma, Tavares Gabriela, Caria Sandra, Barreiros Daniela, Santos Cecília R A
CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal.
CCMAR - Centro de Ciências do Mar, Universidade do Algarve, Faro, Portugal.
FEBS J. 2016 May;283(9):1748-66. doi: 10.1111/febs.13700. Epub 2016 Mar 30.
The olfactory-type signaling machinery has been known to be involved not only in odorant detection but also in other tissues with unsuspected sensory roles. As a barrier, the choroid plexus (CP) is an active participant in the monitoring of the cerebrospinal fluid (CSF), promptly responding to alterations in its composition. We hypothesized that olfactory signaling could be active in CP, contributing to the surveillance of the CSF composition. We determined the mRNA and protein expression of the major components of the olfactory transduction pathway in the rat CP, including odorant receptors, the olfactory G-protein (Gαolf), adenylate cyclase 3 and cyclic nucleotide-gated channel 2. The functionality of the transduction pathway and the intracellular mechanisms involved were analyzed by DC field potential recording electrophysiological analysis, in an ex vivo CP-brain setup, using polyamines as stimuli and blockers of the downstream signaling pathways. Concentration-dependent responses were obtained for the polyamines studied (cadaverine, putrescine, spermine and spermidine), all known to be present in the CSF. Transfection of a CP epithelial cell line with siRNA against Gαolf effectively knocked down protein expression and reduced the CP cells' response to spermine. Thus, the key components of the olfactory chemosensory apparatus are present and are functional in murine CP, and polyamines seem to trigger both the cAMP and the phospholipase C-inositol 1,4,5-trisphosphate pathways. Olfactory-like chemosensory signaling may be an essential component of the CP chemical surveillance apparatus to detect alterations in the CSF composition, and to elicit responses to modulate and maintain brain homeostasis.
已知嗅觉型信号传导机制不仅参与气味检测，还涉及其他具有未被怀疑的感觉作用的组织。脉络丛（CP）作为一道屏障，是监测脑脊液（CSF）的积极参与者，能迅速对其成分变化做出反应。我们推测嗅觉信号可能在脉络丛中活跃，有助于监测脑脊液成分。我们测定了大鼠脉络丛中嗅觉转导途径主要成分的mRNA和蛋白质表达，包括气味受体、嗅觉G蛋白（Gαolf）、腺苷酸环化酶3和环核苷酸门控通道2。在离体脉络丛-脑实验装置中，以多胺作为刺激物和下游信号通路的阻滞剂，通过直流电场电位记录电生理分析来分析转导途径的功能及相关细胞内机制。对所研究的多胺（尸胺、腐胺、精胺和亚精胺）获得了浓度依赖性反应，所有这些多胺在脑脊液中均有存在。用针对Gαolf的小干扰RNA转染脉络丛上皮细胞系可有效降低蛋白质表达，并减少脉络丛细胞对精胺的反应。因此，嗅觉化学感应装置的关键成分在小鼠脉络丛中存在且具有功能，多胺似乎能触发环磷酸腺苷（cAMP）和磷脂酶C-肌醇1,4,5-三磷酸途径。类似嗅觉的化学感应信号可能是脉络丛化学监测装置的重要组成部分，用于检测脑脊液成分的变化，并引发反应以调节和维持脑内稳态。
