Department of Anatomy, Albert Szent-Györgyi Medical School, University of Szeged, Hungary.
Neuroscience. 2010 Feb 3;165(3):749-57. doi: 10.1016/j.neuroscience.2009.10.048. Epub 2009 Oct 27.
The calcium-binding proteins parvalbumin, calbindin D-28k, calretinin and calcineurin are present in subsets of GABAergic gigantic calyciform presynaptic terminals of the reticular thalamic nucleus (RTN). Previously it was hypothesized that GABA and calcium-binding proteins including parvalbumin are not only colocalized in the same neuron subpopulation, but that GABA synthesis and parvalbumin expression could be also genetically regulated by a common mechanism. Moreover, parvalbumin expression levels could influence GABA synthesis. For this, we analyzed GABA immunoreactivity in RTN gigantic calyciform presynaptic terminals of parvalbumin-deficient (PV-/-) mice. With respect to GABA immunoreactivity we found no differences compared to wild-type animals. However, using a polyclonal parvalbumin antibody raised against full-length rat muscle parvalbumin on brain sections of PV-/- mice, we observed paradoxical parvalbumin immunoreactivity in partly varicose axons in the diencephalon, mainly in the lamina medullaris externa surrounding the thalamus. A detailed immunohistochemical, biochemical and molecular biological analysis revealed this immunoreactivity to be the result of an upregulation of oncomodulin (OM), the mammalian beta isoform of parvalbumin in PV-/- mice. In addition, OM was present in a sparse subpopulation of neurons in the thalamus and in the dentate gyrus. OM expression has not been observed before in neurons of the mammalian brain; its expression was restricted to outer hair cells in the organ of Corti. Our results indicate that the absence of parvalbumin has no major effect on the GABA-synthesizing system in RTN presynaptic terminals excluding a direct effect of parvalbumin on this regulation. However, a likely homeostatic mechanism is induced resulting in the upregulation of OM in selected axons and neuronal perikarya. Our results warrant further detailed investigations on the putative role of OM in the brain.
钙结合蛋白 parvalbumin、calbindin D-28k、calretinin 和 calcineurin 存在于网状丘脑核 (RTN) 的 GABA 能巨大钟形 presynaptic 末梢的亚群中。以前的假设是，GABA 和包括 parvalbumin 在内的钙结合蛋白不仅在同一神经元亚群中共同存在，而且 GABA 合成和 parvalbumin 表达也可以通过共同的机制受到遗传调控。此外，parvalbumin 表达水平可能会影响 GABA 合成。为此，我们分析了 parvalbumin 缺陷型 (PV-/-) 小鼠 RTN 巨大钟形 presynaptic 末梢中的 GABA 免疫反应性。与野生型动物相比，我们没有发现 GABA 免疫反应性的差异。然而，在 PV-/- 小鼠的脑切片上，使用针对全长大鼠肌肉 parvalbumin 制备的多克隆 parvalbumin 抗体，我们观察到在间脑的部分曲张轴突中出现了矛盾的 parvalbumin 免疫反应性，主要在围绕丘脑的外髓板外。详细的免疫组织化学、生化和分子生物学分析表明，这种免疫反应性是由于 PV-/- 小鼠中的 oncmodulin (OM) 上调的结果，oncmodulin 是 parvalbumin 的哺乳动物β同工型。此外，OM 存在于丘脑和齿状回中的稀疏神经元亚群中。以前在哺乳动物大脑的神经元中没有观察到 OM 的表达；其表达仅限于 Corti 器官中的外毛细胞。我们的结果表明，parvalbumin 的缺失对 RTN presynaptic 末梢中的 GABA 合成系统没有重大影响，排除了 parvalbumin 对这种调节的直接影响。然而，诱导了一种可能的稳态机制，导致特定轴突和神经元胞体中的 OM 上调。我们的结果表明，有必要进一步详细研究 OM 在大脑中的可能作用。
