Neuroglobin Expression in the Mammalian Auditory System.
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.
Department of Nuclear Medicine, University Medical Center, Johannes Gutenberg-University, Langenbeckstr. 1, Bld. 210, 55101, Mainz, Germany. reuss@uni-mainz.de. Department of Anatomy and Cell Biology, University Medical Center, Johannes Gutenberg-University, 55099, Mainz, Germany. Department of Anatomy and Cell Biology, University Medical Center, Johannes Gutenberg-University, 55099, Mainz, Germany. Department of Anatomy and Cell Biology, University Medical Center, Johannes Gutenberg-University, 55099, Mainz, Germany. Department of Radiation Oncology, University Medical Center, Johannes Gutenberg-University, 55101, Mainz, Germany. Department of ENT, Elbe-Kliniken, 21682, Stade, Germany. Institute of Molecular Genetics, Johannes Gutenberg-University, 55099, Mainz, Germany. Department of Surgery, University of California at San Diego, San Diego, CA, 92093-0604, USA. Veterans Affairs Research Service, VA San Diego Healthcare System, San Diego, CA, 92093-0604, USA. Department of Surgery, University of California at San Diego, San Diego, CA, 92093-0604, USA. Veterans Affairs Research Service, VA San Diego Healthcare System, San Diego, CA, 92093-0604, USA. Institute of Zoology and Zoological Museum, University of Hamburg, Hamburg, Germany. Institute of Molecular Genetics, Johannes Gutenberg-University, 55099, Mainz, Germany. Department of Surgery, University of California at San Diego, San Diego, CA, 92093-0604, USA. Veterans Affairs Research Service, VA San Diego Healthcare System, San Diego, CA, 92093-0604, USA.