Effect of neuregulin-1 on the auditory cortex in adult C57BL/6J mice

Document Type : Original Article

Authors

Department of Otolaryngology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China

Abstract

Objective(s): We sought to explore whether neuregulin-1(NRG1) would have a protective effect on the auditory cortices of adult C57BL/6J mice.
Materials and Methods: We used RTPCR and Western blot (WB) to detect the expression of NRG1 and ERBB4 (the receptor of NRG1) in the auditory cortices of C57BL/6J mice of different ages (6–8 weeks and 42–44 weeks). Three groups of 42–44 week-old C57BL/6J mice were intraperitoneally injected with mouse neurotrophic factor (m-NGF), NRG1, or saline for two months. We observed the ultrastructures of the auditory cortices of adult mice after treatment using transmission electron microscopy. Additionally, we observed expression of NRG1 in the auditory cortices by immunohistochemistry.
Results: Expression of NRG1 and ERBB4 in the auditory cortices of C57BL/6J mice at the age of 42–44 weeks was lower compared with 6–8 week-old mice. The ultra-structures of the auditory cortices, including the neurons and myelin sheaths, as revealed by transmission electron microscopy were healthier in the m-NGF and NRG1 treatment groups than those in the saline group. We found that expression of NRG1 in the auditory cortices after treatment in the m-NGF and NRG1 groups, especially in the NRG1 group, was higher than that in the saline group.
Conclusion: We concluded that with increasing age, NRG1 in the auditory cortices of C57BL/6J mice gradually decreased, and that NRG1 had a protective effect on the auditory cortices in adult C57BL/J mice.

Keywords


1. Gratton MA, Schulte BA, Smythe NM. Quantifcation of the stria vascularis and strial capillary areas in quiet-reared young and aged gerbils. Hear Res 1997; 114: 1-9.
2. Frisina RD, Ding B, Zhu X, Walton JP. Age-related hearing loss: prevention of threshold declines, cell loss and apoptosis in spiral ganglion neurons. Aging (Albany NY) 2016; 8: 2081-2099.
3. Ouda L, Profant O, Syka J. Age-related changes in the central auditory system. Cell Tissue Res. 2015; 361: 337-358.
4. Costa M, Lepore F, Prévost F, Guillemot JP. Effects of aging on peripheral and central auditory processing in rats. Eur J Neurosci 2016; 44: 2084-2094.
5. Brewton DH, Kokash J, Jimenez O, Pena ER, Razak KA. Age-related deterioration of perineuronal nets in the primary auditory cortex of mice. Front Aging Neurosci 2016;8:270.
6. Mei L, Xiong WC. Neuregulin 1 in neural development, synaptic plasticity and schizophrenia. Nat Rev Neurosci 2008; 9: 437-452.
7. Law AJ, Shannon Weickert C, Hyde TM, Kleinman JE, Harrison PJ. Neuregulin-1 (NRG-1) mRNA and protein in the adult human brain. Neuroscience 2004; 127: 125-136.
8. Ozaki M, Itoh K, Miyakawa Y, Kishida H, Hashikawa T. Protein processing and releases of neuregulin-1 are regulated in an activity-dependent manner. J Neurochem 2004; 91: 176-188.
9. Anton ES, Marchionni MA, Lee KF, Rakic P. Role of GGF/neuregulin signaling in interactions between migrating neurons and radial glia in the developing cerebral cortex. Development 1997; 124: 3501-3510.
10. Calaora V, Rogister B, Bismuth K, Murray K, Brandt H, Leprince P, Marchionni M, Dubois-Dalcq M. Neuregulin signaling regulates neural precursor growth and the generation of oligodendrocytes in vitro. J Neurosci 2001; 21: 4740-4751.
11. Lopez-Bendito G, Cautinat A, Sanchez JA, Bielle F, Flames N, Garratt AN, Talmage DA, Role LW, Charnay P, Marin O, Garel S. Tangential neuronal migration controls axon guidance: a role for neuregulin-1 in thalamocortical axon navigation. Cell 2006; 125: 127-142.
12. Gerecke KM, Wyss JM, Carroll SL. Neuregulin-1beta induces neurite extension and arborization in cultured hippocampal neurons. Mol Cell Neurosci 2004; 27: 379-393.
13. Hippenmeyer S, Shneider NA, Birchmeier C, Burden SJ, Jessell TM, Arber S. A role for neuregulin1 signaling in muscle spindle differentiation. Neuron 2002; 36: 1035-1049.
14. Buonanno A, Fischbach GD. Neuregulin and ErbB receptor signaling pathways in the nervous system. Curr Opin Neurobiol 2001; 11: 287-96.
15. Wolpowitz D, Mason TB, Dietrich P, Mendelsohn M, Talmage DA, Role LW. Cysteine-rich domain isoforms of the neuregulin-1 gene are required for maintenance of peripheral synapses. Neuron 2000; 25: 79-91.
16. Escher P, Lacazette E, Courtet M, Blindenbacher A, Landmann L, Bezakova G, Lloyd KC, Mueller U, Brenner HR. Synapses form in skeletal muscles lacking neuregulin receptors. Science 2005; 308: 1920-1923.
17. Jin D, Ohlemiller KK, Lei D, Dong E, Role L, Ryugo DK, Bao J. Age-realted neuronal loss in the cochlea is not delayed by synaptic modulation. Neurobiol Aging 2011; 32: 2321, e13-23.
18. Johnson KR, Erway LC, Cook SA, Willott, JF, Zheng, QY. A major gene affecting age-related hearing loss in C57BL/6J mice. Hear. Res 1997; 114: 83-92.
19. Yu YF, Zhai F, Dai CF, Hu JJ. The relationship between age-related hearing loss and synaptic changes in the hippocampus of C57BL/6J mice. Experimental Gerontology 2011; 46:716-722.
20. Schuknecht HF. Presbycusis. Laryngoscope 1955; 65: 402-419.
21. Nelson EG, Hinojosa R. Presbycusis. A human temporal bone study of individuals with downward sloping audiometric patterns of hearing loss and review of the literature. Laryngoscope 2006; 116: 1-12.
22. Welsh LW, Welsh JJ, Healy MP. Central presbycusis. Laryngoscope 1985; 95: 128-136.
23. Quaranta N, Coppola F, Casulli M, Barulli MR, Panza F, Tortelli R, Capozzo R, Leo A, Tursi M, Grasso A, Solfrizzi V, Sobbà C, Logroscino G. The prevalence of peripheral and central hearing impairment and its relation to cognition in older adults. Audiol Neurootol 2014; 19: 10-14.
24. Fetoni AR, Troiani D, Petrosini L, Paludetti G. Cochlear injury and adaptive plasticity of the auditory cortex. Front Aging Neurosci 2015; 7:8.
25. Chang Y, Lee Sh, Lee YJ, Hwang MJ, Bae SJ, Kim MN, Lee J, Woo S, Lee H, Kang DS. Auditory neural pathway evaluation on sensorineural hearing loss using diffusion tensor imaging. Neuroreport 2004; 15: 1699-1703.
26. Hoeffding V, Feldman ML. Changes with age in the morphology of the cochlear nerve in rats: light microscopy. J Comp Neurol 1988; 276: 537-546.
27. Eckert MA, Cute SL, Vaden KI Jr, Kuchinsky SE, Dubno JR. Auditory cortex signs of age-related hearing loss. J Assoc Res Otolaryngol 2012; 13: 703-713.
28. Wan G, Gomez-Casati ME, Gigliello AR, Liberman MC, Corfas G. Neurotrophin-3 regulates ribbon synapse density in the cochlea and induces synapse regeneration after acoustic trauma. Elife 2014; 3: e03564.
29. Li B, Woo RS, Mei L, Malinow R. The neuregulin-1 receptor erbB4 controls glutamatergic synapse maturation and plasticity. Neuron 2007; 54: 583-597.
30. Bao J, Wolpowitz D, Role LW, Talmage DA. Back signaling by the Nrg-1intracellular domain. J Cell Biol 2003; 161: 1133-1141.
31. Carlsson T, Schindler FR, Höllerhage M, Depboylu C, Arias-Carrión O, Schnurrbusch S, Rösler TW, Wozny W, Schwall GP, Groebe K, Oertel WH, Brundin P, Schrattenholz A, Höglinger GU. Systemic administration of neuregulin-1 β1 protects dopaminergic neurons in a mouse model of Parkinson’s disease. J Neurochem 2011; 117: 1066-1074.
32. Stankovic K, Rio C, Xia A, Sugawara M, Adams JC, Liberman MC, Corfas G. Survival of adult spiral ganglion neurons requires erbB receptor signaling in the inner ear. J Neurosci 2004; 24: 8651-8661.
33. Xu J, Hu C, Chen S, Shen H, Jiang Q, Huang P, Zhao W. Neuregulin-1 protects mouse cerebellum against oxidative stress and neuroinflammation. Brain Res 2017; 1670: 32-43.
34. Han Z, Wang CP, Cong N, Gu YY, Ma R, Chi FL. Therapeutic value of nerve growth factor in promoting neural stem cell survival and differentiation and protecting against neuronal hearing loss. Mol Cell Biochem 2017; 428: 149-159.
35. Gao L, Ge R, Xie G, Yao D, Li P, Wang O, Ma X, Han F. Hearing improvement in A/J mice via the mouse nerve growth factor. Clin Exp Otorhinolaryngol 2017; 10: 303-308.