title: Neuroglobin Expression in the Mammalian Auditory System.
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.
authors: Department of Nuclear Medicine, University Medical Center, Johannes Gutenberg-University, Langenbeckstr. 1, Bld. 210, 55101, Mainz, Germany. reuss@uni-mainz.de.
authors: Stefan
authors: S
authors: Reuss
authors: Department of Anatomy and Cell Biology, University Medical Center, Johannes Gutenberg-University, 55099, Mainz, Germany.
authors: Ovidiu
authors: O
authors: Banica
authors: Department of Anatomy and Cell Biology, University Medical Center, Johannes Gutenberg-University, 55099, Mainz, Germany.
authors: Mirra
authors: M
authors: Elgurt
authors: Department of Anatomy and Cell Biology, University Medical Center, Johannes Gutenberg-University, 55099, Mainz, Germany.
authors: Stephanie
authors: S
authors: Mitz
authors: Department of Radiation Oncology, University Medical Center, Johannes Gutenberg-University, 55101, Mainz, Germany.
authors: Ursula
authors: U
authors: Disque-Kaiser
authors: Department of ENT, Elbe-Kliniken, 21682, Stade, Germany.
authors: Randolf
authors: R
authors: Riemann
authors: Institute of Molecular Genetics, Johannes Gutenberg-University, 55099, Mainz, Germany.
authors: Marco
authors: M
authors: Hill
authors: 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.
authors: Dawn V
authors: DV
authors: Jaquish
authors: 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.
authors: Fred J
authors: FJ
authors: Koehrn
authors: Institute of Zoology and Zoological Museum, University of Hamburg, Hamburg, Germany.
authors: Thorsten
authors: T
authors: Burmester
authors: Institute of Molecular Genetics, Johannes Gutenberg-University, 55099, Mainz, Germany.
authors: Thomas
authors: T
authors: Hankeln
authors: 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.
authors: Nigel K
authors: NK
authors: Woolf
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000368:Aged; D000818:Animals; D001933:Brain Stem / Q000378:metabolism*; D003051:Cochlea / Q000378:metabolism*; D005260:Female; D005914:Globins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D000078787:Neuroglobin; D052248:Nitric Oxide Synthase Type I / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013136:Spiral Ganglion / Q000378:metabolism; D065832:Superior Olivary Complex / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D000255:Adenosine Triphosphate; D005914:Globins; D052248:Nitric Oxide Synthase Type I
keywords: Auditory; Cochlea; Hair cell; Hearing; Mice; Neuroglobin; Spiral ganglion
references: Acta Physiol (Oxf). 2014 Jul;211(3):501-14
references: 24811692
references: J Otolaryngol. 2001 Apr;30(2):106-14
references: 11770952
references: Biochim Biophys Acta. 2013 Sep;1834(9):1772-8
references: 23639750
references: Br J Ophthalmol. 2007 May;91(5):663-6
references: 17151062
references: Mol Biol Evol. 2012 Apr;29(4):1105-14
references: 22115833
references: Curr Opin Otolaryngol Head Neck Surg. 2010 Oct;18(5):447-53
references: 20717032
references: J Exp Biol. 2009 May;212(Pt 10):1423-8
references: 19411534
references: Neuroendocrinology. 2008;88(3):173-82
references: 18451642
references: Mol Biol Evol. 2002 Apr;19(4):416-21
references: 11919282
references: Neurosci Lett. 2004 May 20;362(2):83-6
references: 15193759
references: J Biol Chem. 2002 May 31;277(22):19538-45
references: 11893755
references: Hear Res. 2011 Sep;279(1-2):1-12
references: 21187136
references: Anat Embryol (Berl). 1992;185(1):1-16
references: 1736680
references: J Comp Neurol. 2003 Feb 3;456(2):105-11
references: 12509868
references: J Histochem Cytochem. 1981 Apr;29(4):577-80
references: 6166661
references: J Biol Chem. 2001 Oct 19;276(42):38949-55
references: 11473128
references: Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8483-8
references: 15932948
references: Clin Otolaryngol Allied Sci. 1997 Oct;22(5):394-402
references: 9372248
references: Brain Res Brain Res Rev. 2003 Sep;43(1):17-28
references: 14499459
references: Laryngoscope. 1972 Dec;82(12):2249-72
references: 4539701
references: Hear Res. 1984 Aug;15(2):113-21
references: 6490538
references: Pflugers Arch. 2009 Apr;457(6):1303-25
references: 18777041
references: J Biol Chem. 2003 Aug 15;278(33):30417-20
references: 12796507
references: Proc Natl Acad Sci U S A. 2010 Dec 14;107(50):21570-5
references: 21115824
references: FEBS J. 2008 Jul;275(14):3633-43
references: 18537818
references: J Biol Chem. 2005 May 27;280(21):20660-5
references: 15793311
references: Science. 1985 Jan 11;227(4683):194-6
references: 3966153
references: Acta Otolaryngol. 1972 Feb-Mar;73(2):235-48
references: 5015157
references: Hear Res. 2002 Jun;168(1-2):12-24
references: 12117505
references: Anat Rec (Hoboken). 2009 Apr;292(4):461-71
references: 19301282
references: Brain Res. 1999 Oct 30;846(1):106-11
references: 10536217
references: Microsc Res Tech. 2000 Nov 15;51(4):403-12
references: 11071722
references: Cytogenet Genome Res. 2006;112(3-4):296-306
references: 16484786
references: Mol Biol Evol. 2005 Jan;22(1):12-20
references: 15356282
references: Neurosci Lett. 2003 Jul 31;346(1-2):114-6
references: 12850561
references: Laryngoscope. 1972 Nov;82(11):2059-78
references: 5081743
references: IUBMB Life. 2004 Nov-Dec;56(11-12):703-7
references: 15804835
references: IUBMB Life. 2004 Nov-Dec;56(11-12):671-9
references: 15804831
references: Hear Res. 1994 Sep;79(1-2):39-47
references: 7528738
references: Nature. 2000 Sep 28;407(6803):520-3
references: 11029004
references: Exp Transl Stroke Med. 2012 Aug 20;4(1):15
references: 22901501
references: Philos Trans R Soc Lond B Biol Sci. 1994 Jul 29;345(1312):175-221
references: 7526408
references: Hear Res. 2012 Nov;293(1-2):12-20
references: 22633944
references: Am J Otolaryngol. 1988 Nov-Dec;9(6):278-90
references: 3067591
references: J Histochem Cytochem. 2002 Dec;50(12):1591-8
references: 12486081
references: Hear Res. 1999 Sep;135(1-2):181-9
references: 10491966
references: Hear Res. 2003 Nov;185(1-2):65-76
references: 14599694
references: Cell Mol Life Sci. 2007 May;64(10):1259-68
references: 17385072
references: J Comp Neurol. 2000 Jun 19;422(1):95-105
references: 10842220
references: Neuroscience. 2012 Oct 25;223:35-44
references: 22864183
references: Prog Retin Eye Res. 2001 Mar;20(2):175-208
references: 11173251
references: J Inorg Biochem. 2005 Jan;99(1):110-9
references: 15598495
references: Neuroscience. 2009 Oct 6;163(2):552-60
references: 19576963
references: Brain Res. 2010 Apr 23;1327:56-68
references: 20211612
references: J Comp Neurol. 1999 Feb 1;404(1):52-63
references: 9886024
references: Physiol Rev. 2001 Apr;81(2):569-628
references: 11274340
references: J Neurochem. 1970 Oct;17(10):1501-4
references: 4919436
references: Brain Res Bull. 2003 Jun 15;60(5-6):397-422
references: 12787864
references: J Neurophysiol. 1988 Nov;60(5):1779-98
references: 3199181
references: Neurosci Lett. 2005 Feb 21;374(3):207-11
references: 15663964
references: Brain Res. 1998 Sep 14;805(1-2):181-90
references: 9733963
references: Exp Brain Res. 1988;71(2):241-51
references: 3169161
references: J Exp Biol. 2003 Jun;206(Pt 12):2011-20
references: 12756283
references: Neuroscience. 2002;115(3):645-56
references: 12435404
references: Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):15306-11
references: 11742077
references: J Biol Chem. 2003 Jan 17;278(3):1932-5
references: 12409290
references: Brain Res. 2010 May 17;1331:58-73
references: 20331985
references: Arch Otorhinolaryngol. 1987;244(5):273-7
references: 3439916
references: Biochem Biophys Res Commun. 2004 Dec 17;325(3):719-25
references: 15541349
references: J Histochem Cytochem. 1974 Dec;22(12):1077-83
references: 4374474
references: Hear Res. 1997 Dec;114(1-2):102-6
references: 9447924
references: J Biol Chem. 2001 Jul 6;276(27):25318-23
references: 11320098
references: Hear Res. 1997 Jun;108(1-2):89-111
references: 9213126
references: Anat Rec. 1946 Feb;94:239-47
references: 21015608
references: Biochim Biophys Acta. 2013 Sep;1834(9):1801-12
references: 23360762
references: Invest Ophthalmol Vis Sci. 2006 Mar;47(3):1016-23
references: 16505036
references: Hear Res. 2007 May;227(1-2):19-27
references: 17079104
references: Hear Res. 1984 Sep;15(3):215-24
references: 6501111
references: Brain Res. 1982 Feb 25;234(2):213-25
references: 7059827
references: Brain Res Bull. 2007 Mar 15;71(5):529-38
references: 17259023
references: Acta Otolaryngol. 1986 Jan-Feb;101(1-2):75-87
references: 3515842
references: Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3497-500
references: 12621155
references: J Neurophysiol. 2005 Jan;93(1):557-69
references: 15456804
references: Arch Otorhinolaryngol. 1981;233(1):89-97
references: 6976165
references: J Comp Neurol. 1983 Sep 10;219(2):203-14
references: 6619338
references: J Comp Neurol. 1991 Apr 15;306(3):393-408
references: 1865000
references: Neuroendocrinology. 2008;88(3):183-98
references: 18509243