Reuss Stefan, Banica Ovidiu, Elgurt Mirra, Mitz Stephanie, Disque-Kaiser Ursula, Riemann Randolf, Hill Marco, Jaquish Dawn V, Koehrn Fred J, Burmester Thorsten, Hankeln Thomas, Woolf Nigel K
Department of Nuclear Medicine, University Medical Center, Johannes Gutenberg-University, Langenbeckstr. 1, Bld. 210, 55101, Mainz, Germany.
Department of Anatomy and Cell Biology, University Medical Center, Johannes Gutenberg-University, 55099, Mainz, Germany.
Mol Neurobiol. 2016 Apr;53(3):1461-1477. doi: 10.1007/s12035-014-9082-1. Epub 2015 Jan 31.
The energy-yielding pathways that provide the large amounts of metabolic energy required by inner ear sensorineural cells are poorly understood. Neuroglobin (Ngb) is a neuron-specific hemoprotein of the globin family, which is suggested to be involved in oxidative energy metabolism. Here, we present quantitative real-time reverse transcription PCR, in situ hybridization, immunohistochemical, and Western blot evidence that neuroglobin is highly expressed in the mouse and rat cochlea. For primary cochlea neurons, Ngb expression is limited to the subpopulation of type I spiral ganglion cells, those which innervate inner hair cells, while the subpopulation of type II spiral ganglion cells which innervate the outer hair cells do not express Ngb. We further investigated Ngb distribution in rat, mouse, and human auditory brainstem centers, and found that the cochlear nuclei and superior olivary complex (SOC) also express considerable amounts of Ngb. Notably, the majority of olivocochlear neurons, those which provide efferent innervation of outer hair cells as identified by neuronal tract tracing, were Ngb-immunoreactive. We also observed that neuroglobin in the SOC frequently co-localized with neuronal nitric oxide synthase, the enzyme responsible for nitric oxide production. Our findings suggest that neuroglobin is well positioned to play an important physiologic role in the oxygen homeostasis of the peripheral and central auditory nervous system, and provides the first evidence that Ngb signal differentiates the central projections of the inner and outer hair cells.
内耳感觉神经细胞所需大量代谢能量的产能途径目前了解甚少。神经球蛋白(Ngb)是球蛋白家族的一种神经元特异性血红蛋白,据推测其参与氧化能量代谢。在此,我们提供了定量实时逆转录PCR、原位杂交、免疫组织化学和蛋白质印迹证据,表明神经球蛋白在小鼠和大鼠耳蜗中高度表达。对于原代耳蜗神经元,Ngb表达仅限于支配内毛细胞的I型螺旋神经节细胞亚群,而支配外毛细胞的II型螺旋神经节细胞亚群不表达Ngb。我们进一步研究了Ngb在大鼠、小鼠和人类听觉脑干中枢的分布,发现耳蜗核和上橄榄复合体(SOC)也表达相当数量的Ngb。值得注意的是,通过神经束追踪鉴定为提供外毛细胞传出神经支配的大多数橄榄耳蜗神经元具有Ngb免疫反应性。我们还观察到,SOC中的神经球蛋白经常与神经元型一氧化氮合酶共定位,该酶负责一氧化氮的产生。我们的研究结果表明,神经球蛋白在周围和中枢听觉神经系统的氧稳态中很可能发挥重要的生理作用,并提供了首个证据表明Ngb信号可区分内毛细胞和外毛细胞的中枢投射。