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Neuroglobin Expression in the Mammalian Auditory System

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Abstract

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.

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Abbreviations

pb:

Base pairs

DPO:

Dorsal paraolivary nucleus

FG:

Fluoro-Gold

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

IHC:

Inner hair cells

ISH:

In situ hybridization

LOC/MOC:

Lateral/medial olivocochlear neurons

LSO:

Lateral superior olive

MNTB:

Medial nucleus of the trapezoid body

MSO:

Medial superior olive

Ngb:

Neuroglobin

nNOS:

Neuronal nitric oxide synthase

NO:

Nitric oxide

OHC:

Outer hair cells

OCN:

Olivocochlear neurons

PBS:

Phosphate-buffered 0.9 % saline

RPO:

Rostral paraolivary nucleus

rt-RT-PCR:

Real-time reverse transcription polymerase chain-reaction

RT:

Room temperature

Sgn:

Spiral ganglion neurons

SOC:

Superior olivary complex

SPO:

Superior paraolivary nucleus

VNTB:

Ventral nucleus of the trapezoid body

VPO:

Ventral paraolivary nucleus

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Acknowledgments

This work was supported by grants from the National Institutes of Health, National Institute for Deafness and Communication Disorders grants DC00386 and DC02666, and the Research Service of the Department of Veterans Affairs (USA), from the Röttger-Stiftung and Hoffmann-Klose-Stiftung (Germany) and by the Deutsche Forschungsgemeinschaft (Bu956/5 and Ha2103/3). We thank Dr. Thorsten Fink, Department of Pathology, HSK Wiesbaden, Germany, for providing the human brainstem specimens. The University of California Cancer Center Biomedical Imaging Core is also thanked for their imaging support. We thank Steve McMullen of the UCSD Cancer Center Digital Imaging Shared Resource for his assistance in collecting the deconvolution digital microscope images; Anuradha Desai of the Department of Surgery, University of California at San Diego and the Veterans Affairs Research Service, VA San Diego Healthcare System, CA, for her technical assistance with the Western blot assays; and Kunlin Jin and David A. Greenberg of Buck Institute for Age Research, Novato, CA, for their helpful discussions and comments.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Nuclear Medicine, University Medical Center, Johannes Gutenberg-University, Langenbeckstr. 1, Bld. 210, 55101, Mainz, Germany

    Stefan Reuss

  2. Department of Anatomy and Cell Biology, University Medical Center, Johannes Gutenberg-University, 55099, Mainz, Germany

    Ovidiu Banica, Mirra Elgurt & Stephanie Mitz

  3. Department of Radiation Oncology, University Medical Center, Johannes Gutenberg-University, 55101, Mainz, Germany

    Ursula Disque-Kaiser

  4. Department of ENT, Elbe-Kliniken, 21682, Stade, Germany

    Randolf Riemann

  5. Institute of Molecular Genetics, Johannes Gutenberg-University, 55099, Mainz, Germany

    Marco Hill & Thomas Hankeln

  6. Department of Surgery, University of California at San Diego, San Diego, CA, 92093-0604, USA

    Dawn V. Jaquish, Fred J. Koehrn & Nigel K. Woolf

  7. Veterans Affairs Research Service, VA San Diego Healthcare System, San Diego, CA, 92093-0604, USA

    Dawn V. Jaquish, Fred J. Koehrn & Nigel K. Woolf

  8. Institute of Zoology and Zoological Museum, University of Hamburg, Hamburg, Germany

    Thorsten Burmester

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Correspondence to Stefan Reuss.

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Reuss, S., Banica, O., Elgurt, M. et al. Neuroglobin Expression in the Mammalian Auditory System. Mol Neurobiol 53, 1461–1477 (2016). https://doi.org/10.1007/s12035-014-9082-1

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