Serotonergic innervation of respiratory motor nuclei after cervical spinal injury: Impact of intermittent hypoxia.
Animals
Cervical Cord
/ metabolism
Cervical Vertebrae
Hypoxia
Intercostal Nerves
/ metabolism
Male
Motor Neurons
/ physiology
Nerve Regeneration
/ physiology
Phrenic Nerve
/ metabolism
Rats
Rats, Sprague-Dawley
Recovery of Function
/ physiology
Serotonin
/ metabolism
Spinal Cord Injuries
/ metabolism
Cervical hemisection
Intercostal motor neurons
Intermittent hypoxia
Phrenic motor neurons
Raphe
Serotonin
Spinal cord injury
Journal
Experimental neurology
ISSN: 1090-2430
Titre abrégé: Exp Neurol
Pays: United States
ID NLM: 0370712
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
received:
29
06
2020
revised:
31
12
2020
accepted:
09
01
2021
pubmed:
19
1
2021
medline:
18
9
2021
entrez:
18
1
2021
Statut:
ppublish
Résumé
Although cervical spinal cord injury (cSCI) disrupts bulbo-spinal serotonergic projections, partial recovery of spinal serotonergic innervation below the injury site is observed after incomplete cSCI. Since serotonin contributes to functional recovery post-injury, treatments to restore or accelerate serotonergic reinnervation are of considerable interest. Intermittent hypoxia (IH) was reported to increase serotonin innervation near respiratory motor neurons in spinal intact rats, and to improve function after cSCI. Here, we tested the hypotheses that spontaneous serotonergic reinnervation of key respiratory (phrenic and intercostal) motor nuclei: 1) is partially restored 12 weeks post C2 hemisection (C2Hx); 2) is enhanced by IH; and 3) results from sprouting of spared crossed-spinal serotonergic projections below the site of injury. Serotonin was assessed via immunofluorescence in male Sprague Dawley rats with and without C2Hx (12 wks post-injury); individual groups were exposed to 28 days of: 1) normoxia; 2) daily acute IH (dAIH28: 10, 5 min 10.5% O2 episodes per day; 5 min normoxic intervals); 3) mild chronic IH (IH28-5/5: 5 min 10.5% O2 episodes; 5 min intervals; 8 h/day); or 4) moderate chronic IH (IH28-2/2: 2 min 10.5% O2 episodes; 2 min intervals; 8 h/day), simulating IH experienced during moderate sleep apnea. After C2Hx, the number of ipsilateral serotonergic structures was decreased in both motor nuclei, regardless of IH protocol. However, serotonergic structures were larger after C2Hx in both motor nuclei, and total serotonin immunolabeling area was increased in the phrenic motor nucleus but reduced in the intercostal motor nucleus. Both chronic IH protocols increased serotonin structure size and total area in the phrenic motor nuclei of uninjured rats, but had no detectable effects after C2Hx. Although the functional implications of fewer but larger serotonergic structures are unclear, we confirm that serotonergic reinnervation is substantial following injury, but IH does not affect the extent of reinnervation.
Identifiants
pubmed: 33460645
pii: S0014-4886(21)00014-5
doi: 10.1016/j.expneurol.2021.113609
pmc: PMC8327480
mid: NIHMS1722482
pii:
doi:
Substances chimiques
Serotonin
333DO1RDJY
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
113609Subventions
Organisme : NIH HHS
ID : OT2 OD023854
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL147554
Pays : United States
Organisme : NICHD NIH HHS
ID : T32 HD043730
Pays : United States
Organisme : NICHD NIH HHS
ID : K12 HD055929
Pays : United States
Organisme : NHLBI NIH HHS
ID : R37 HL069064
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL069064
Pays : United States
Informations de copyright
Copyright © 2021. Published by Elsevier Inc.
Références
J Physiol. 2009 Nov 15;587(Pt 22):5469-81
pubmed: 19805745
J Neurotrauma. 2015 Jun 15;32(12):893-907
pubmed: 25625912
Neurology. 2014 Jan 14;82(2):104-13
pubmed: 24285617
J Neurosci. 2002 Jul 15;22(14):6239-46
pubmed: 12122082
J Neurosci. 1995 Dec;15(12):7929-39
pubmed: 8613731
J Neurosci. 2012 Mar 14;32(11):3591-600
pubmed: 22423083
Eur J Neurosci. 2008 Dec;28(12):2365-70
pubmed: 19087167
J Appl Physiol (1985). 2014 Jul 15;117(2):180-8
pubmed: 24833779
J Neurosci. 1998 Oct 15;18(20):8436-43
pubmed: 9763486
Exp Neurol. 2017 Jan;287(Pt 2):93-101
pubmed: 27079999
Exp Neurol. 2008 May;211(1):97-106
pubmed: 18308305
Arch Phys Med Rehabil. 2005 Jun;86(6):1193-9
pubmed: 15954059
J Neurosci. 2001 Jul 15;21(14):5381-8
pubmed: 11438615
Biomark Insights. 2010 Feb 09;5:9-20
pubmed: 20212918
J Physiol. 1993 Feb;461:213-33
pubmed: 8350262
Neuroscience. 2010 Aug 25;169(2):787-93
pubmed: 20478365
Respir Physiol Neurobiol. 2018 Oct;256:50-57
pubmed: 28549897
Chest. 2019 Feb;155(2):438-445
pubmed: 30321507
Exp Neurol. 2019 Aug;318:174-191
pubmed: 31085200
J Neurosci. 2015 Apr 29;35(17):6871-80
pubmed: 25926462
Experientia. 1964 Jul 15;20(7):398-9
pubmed: 5856530
Neuroscience. 1981;6(4):557-618
pubmed: 7017455
J Neurosci. 2011 May 25;31(21):7682-90
pubmed: 21613481
Ann N Y Acad Sci. 2010 Jun;1198:252-9
pubmed: 20536940
Curr Pharm Des. 2013;19(24):4371-84
pubmed: 23360270
Am J Phys Med Rehabil. 2003 Oct;82(10):803-14
pubmed: 14508412
Dan Med J. 2016 Feb;63(2):
pubmed: 26836802
J Neurosci. 2000 Jan 15;20(2):771-82
pubmed: 10632606
Physiology (Bethesda). 2014 Jan;29(1):39-48
pubmed: 24382870
Am J Physiol Regul Integr Comp Physiol. 2014 Nov 15;307(10):R1181-97
pubmed: 25231353
J Appl Physiol (1985). 2015 Dec 15;119(12):1455-65
pubmed: 25997947
J Physiol. 2018 Apr 15;596(8):1501-1512
pubmed: 29388230
Exp Neurol. 1996 Jun;139(2):203-13
pubmed: 8654523
Ann N Y Acad Sci. 1990;600:9-34; discussion 34-5
pubmed: 2252340
Prog Brain Res. 1982;57:239-65
pubmed: 6296918
Exp Neurol. 2015 Apr;266:1-10
pubmed: 25687551
Physiol Rev. 1992 Jan;72(1):165-229
pubmed: 1731370
Sleep. 2008 Aug;31(8):1071-8
pubmed: 18714778
Annu Rev Neurosci. 2003;26:239-66
pubmed: 12598679
Am J Physiol Regul Integr Comp Physiol. 2018 Jan 1;314(1):R135-R144
pubmed: 29021191
J Neurosci. 1990 Apr;10(4):1091-8
pubmed: 2329370
J Appl Physiol (1985). 2003 Feb;94(2):795-810
pubmed: 12531916
J Comp Neurol. 1997 Oct 6;386(4):613-24
pubmed: 9378855
J Appl Physiol (1985). 2001 Jun;90(6):2466-75
pubmed: 11356815
J Clin Sleep Med. 2014 Jan 15;10(1):65-72
pubmed: 24426822
Mol Pain. 2015 Jul 16;11:42
pubmed: 26173454
J Appl Physiol (1985). 2000 Oct;89(4):1528-36
pubmed: 11007592
J Neurosci. 2005 Mar 16;25(11):2925-32
pubmed: 15772352
Brain Res. 1981 Dec 7;226(1-2):187-99
pubmed: 7028211
J Neurosci Methods. 2009 Sep 15;182(2):244-9
pubmed: 19559048
Sleep. 1999 Aug 1;22(5):667-89
pubmed: 10450601
Respir Physiol Neurobiol. 2019 Mar;261:15-23
pubmed: 30590202
Neuroscience. 1985 Jun;15(2):445-80
pubmed: 4022334
Exp Neurol. 2012 Sep;237(1):103-15
pubmed: 22704858
Brain Res. 1991 Jan 25;539(2):263-70
pubmed: 1829012
Eur J Neurosci. 2004 Sep;20(5):1161-76
pubmed: 15341588