Altered expression of genes regulating inflammation and synaptogenesis during regrowth of afferent neurons to cochlear hair cells.
Animals
Animals, Newborn
Gene Expression
/ drug effects
Hair Cells, Auditory
/ drug effects
Inflammation
/ genetics
Kainic Acid
/ toxicity
Mice
Mice, Inbred C57BL
Models, Neurological
Nerve Regeneration
/ genetics
Neurogenesis
/ genetics
Neurons, Afferent
/ physiology
Spiral Ganglion
/ cytology
Synapses
/ physiology
Tissue Culture Techniques
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2020
2020
Historique:
received:
07
04
2020
accepted:
19
08
2020
entrez:
1
10
2020
pubmed:
2
10
2020
medline:
18
11
2020
Statut:
epublish
Résumé
The spiral ganglion neurons constitute the primary connection between auditory hair cells and the brain. The spiral ganglion afferent fibers and their synapse with hair cells do not regenerate to any significant degree in adult mammalian ears after damage. We have investigated gene expression changes after kainate-induced disruption of the synapses in a neonatal cochlear explant model in which peripheral fibers and the afferent synapse do regenerate. We compared gene expression early after damage, during regeneration of the fibers and synapses, and after completion of in vitro regeneration. These analyses revealed a total of 2.5% differentially regulated transcripts (588 out of 24,000) based on a threshold of p<0.005. Inflammatory response genes as well as genes involved in regeneration of neural circuits were upregulated in the spiral ganglion neurons and organ of Corti, where the hair cells reside. Prominent genes upregulated at several time points included genes with roles in neurogenesis (Elavl4 and Sox21), neural outgrowth (Ntrk3 and Ppp1r1c), axonal guidance (Rgmb and Sema7a), synaptogenesis (Nlgn2 and Psd2), and synaptic vesicular function (Syt8 and Syn1). Immunohistochemical and in situ hybridization analysis of genes that had not previously been described in the cochlea confirmed their cochlear expression. The time course of expression of these genes suggests that kainate treatment resulted in a two-phase response in spiral ganglion neurons: an acute response consistent with inflammation, followed by an upregulation of neural regeneration genes. Identification of the genes activated during regeneration of these fibers suggests candidates that could be targeted to enhance regeneration in adult ears.
Identifiants
pubmed: 33001981
doi: 10.1371/journal.pone.0238578
pii: PONE-D-20-10023
pmc: PMC7529247
doi:
Substances chimiques
Kainic Acid
SIV03811UC
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0238578Subventions
Organisme : NIDCD NIH HHS
ID : R01 DC015824
Pays : United States
Organisme : NIDCD NIH HHS
ID : R01 DC007174
Pays : United States
Déclaration de conflit d'intérêts
Dr. Edge acknowledges a competing interest as a cofounder and consultant to Decibel Therapeutics and Audion Therapeutics. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
Références
Exp Brain Res. 1979 Jan 15;34(2):389-93
pubmed: 217706
Genes Dev. 2001 Apr 1;15(7):877-88
pubmed: 11297511
Neurochem Res. 2011 Jul;36(7):1261-9
pubmed: 21287267
J Neurosci. 2010 Sep 15;30(37):12387-99
pubmed: 20844134
Development. 2007 Aug;134(16):2925-33
pubmed: 17626062
Dev Biol. 2015 Jan 15;397(2):237-47
pubmed: 25448693
Acta Otolaryngol. 1993 May;113(3):330-4
pubmed: 8100108
Hear Res. 1989 Nov;42(2-3):167-73
pubmed: 2481667
Neuron. 1999 Oct;24(2):377-87
pubmed: 10571231
J Neurobiol. 2006 Mar;66(4):319-31
pubmed: 16408287
Hear Res. 1985 May;18(2):145-51
pubmed: 2864329
J Vis Exp. 2010 Feb 04;(36):
pubmed: 20134402
Acta Otolaryngol. 1971 Feb-Mar;71(2):166-76
pubmed: 5577011
J Cell Sci. 2013 Jan 15;126(Pt 2):542-53
pubmed: 23203807
Nature. 1998 Jul 16;394(6690):281-4
pubmed: 9685158
PLoS One. 2013 Apr 24;8(4):e61462
pubmed: 23637839
J Cell Biol. 1995 Mar;128(5):905-12
pubmed: 7876313
J Neurosci. 2011 May 25;31(21):7938-49
pubmed: 21613508
Acta Otolaryngol. 1997 Mar;117(2):214-8
pubmed: 9105452
Nat Protoc. 2009;4(1):44-57
pubmed: 19131956
PLoS One. 2015 Feb 18;10(2):e0117264
pubmed: 25692578
Dev Neurobiol. 2014 Apr;74(4):457-66
pubmed: 24123853
Biochim Biophys Acta. 2006 Jan;1763(1):73-81
pubmed: 16386321
Dev Dyn. 2012 Dec;241(12):1886-900
pubmed: 23073896
RNA. 2013 Aug;19(8):1019-37
pubmed: 23861535
Stem Cells Dev. 2013 Mar 15;22(6):901-12
pubmed: 23078657
Dev Cell. 2012 Dec 11;23(6):1230-7
pubmed: 23168169
J Neurosci. 2012 Sep 5;32(36):12543-57
pubmed: 22956844
Nature. 2009 Oct 22;461(7267):1126-9
pubmed: 19847265
J Neurosci. 2001 Aug 15;21(16):6170-80
pubmed: 11487640
Nat Genet. 2000 May;25(1):25-9
pubmed: 10802651
Am J Pathol. 2013 Sep;183(3):820-30
pubmed: 23850082
Glia. 2019 Jun;67(6):1167-1178
pubmed: 30730592
J Assoc Res Otolaryngol. 2013 Jun;14(3):321-9
pubmed: 23423560
J Neurosci. 2014 Feb 5;34(6):2191-202
pubmed: 24501359
Development. 2014 Feb;141(4):816-29
pubmed: 24496619
Dev Neurobiol. 2007 Feb 15;67(3):316-25
pubmed: 17443790
J Neurosci. 2009 Nov 11;29(45):14077-85
pubmed: 19906956
Trends Cell Biol. 2014 Feb;24(2):128-35
pubmed: 24029244
Semin Cell Dev Biol. 2013 Mar;24(3):129-38
pubmed: 23333497
J Biol Chem. 2010 Jan 1;285(1):392-400
pubmed: 19864427
Hear Res. 1983 Mar;9(3):263-78
pubmed: 6841283
Invest Ophthalmol Vis Sci. 2012 Jul 09;53(8):4575-85
pubmed: 22700709
Anticancer Res. 2002 Nov-Dec;22(6C):4081-5
pubmed: 12553036
J Neurosci. 2009 Nov 4;29(44):13883-97
pubmed: 19889999
Annu Rev Biochem. 2003;72:609-42
pubmed: 12676795
Hear Res. 2010 Jun 14;265(1-2):83-9
pubmed: 20146935
Neural Regen Res. 2015 May;10(5):710-2
pubmed: 26109941
J Neurosci. 2006 Mar 29;26(13):3541-50
pubmed: 16571762
J Neurochem. 2005 May;93(3):674-85
pubmed: 15836626
Neuron. 2006 Sep 21;51(6):741-54
pubmed: 16982420
Acta Otolaryngol Suppl. 1990;476:32-6
pubmed: 1982389
Front Neurol. 2019 Sep 11;10:977
pubmed: 31632328
J Neurosci. 2000 May 15;20(10):3736-44
pubmed: 10804215
J Neurosci. 2011 Jul 27;31(30):10903-18
pubmed: 21795542
Neuroscience. 2019 May 21;407:8-20
pubmed: 30099118
Biochem Biophys Res Commun. 2009 May 15;382(4):795-800
pubmed: 19324014
J Neurochem. 1998 Aug;71(2):749-56
pubmed: 9681466
J Neurosci. 2012 Jul 25;32(30):10352-64
pubmed: 22836268
Nat Cell Biol. 2004 Aug;6(8):756-62
pubmed: 15258590
J Neurosci. 2006 Feb 15;26(7):2115-23
pubmed: 16481444
J Neurosci. 2011 Dec 14;31(50):18391-400
pubmed: 22171041
Neuron. 2012 May 24;74(4):691-705
pubmed: 22632727
Anat Rec (Hoboken). 2012 Nov;295(11):1877-95
pubmed: 23044862
J Neurosci. 2011 May 18;31(20):7275-90
pubmed: 21593312
J Neurosci Res. 2005 Mar 1;79(5):644-51
pubmed: 15672440