Minocycline attenuates ethanol-induced cell death and microglial activation in the developing spinal cord.
Animals
Anti-Bacterial Agents
/ pharmacology
Apoptosis
/ drug effects
Caspase 3
/ metabolism
Cytokines
/ metabolism
Ethanol
/ adverse effects
Female
Glycogen Synthase Kinase 3 beta
/ metabolism
MAP Kinase Signaling System
Male
Mice
Microglia
/ drug effects
Minocycline
/ pharmacology
Neurogenic Inflammation
/ drug therapy
Proto-Oncogene Proteins c-akt
/ metabolism
Spinal Cord
/ drug effects
TOR Serine-Threonine Kinases
/ metabolism
Alcohol
Fetal alcohol spectrum disorders
Glycogen synthase kinase 3
Inflammation
Neuroprotection
Journal
Alcohol (Fayetteville, N.Y.)
ISSN: 1873-6823
Titre abrégé: Alcohol
Pays: United States
ID NLM: 8502311
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
10
07
2018
revised:
03
12
2018
accepted:
04
12
2018
pubmed:
12
12
2018
medline:
22
7
2020
entrez:
12
12
2018
Statut:
ppublish
Résumé
Developmental exposure to ethanol may cause fetal alcohol spectrum disorders (FASD), and the immature central nervous system (CNS) is particularly vulnerable to ethanol. In addition to vulnerability in the developing brain, we previously showed that ethanol also caused neuroapoptosis, microglial activation, and neuroinflammation in the spinal cord. Minocycline is an antibiotic that inhibits microglial activation and alleviates neuroinflammation. We sought to determine whether minocycline could protect spinal cord neurons against ethanol-induced damage. In this study, we showed that minocycline significantly inhibited ethanol-induced caspase-3 activation, microglial activation, and the expression of pro-inflammatory cytokines in the developing spinal cord. Moreover, minocycline blocked ethanol-induced activation of glycogen synthase kinase 3 beta (GSK3β), a key regulator of microglial activation. Meanwhile, minocycline significantly restored ethanol-induced inhibition of protein kinase B (AKT), mammalian target of the rapamycin (mTOR), and ERK1/2 signaling pathways, which were important pro-survival signaling pathways for neurons. Together, minocycline may attenuate ethanol-induced damage to the developing spinal cord by inhibiting microglial activation/neuroinflammation and by restoring the pro-survival signaling.
Identifiants
pubmed: 30529756
pii: S0741-8329(18)30204-0
doi: 10.1016/j.alcohol.2018.12.002
pmc: PMC6555701
mid: NIHMS1516173
pii:
doi:
Substances chimiques
Anti-Bacterial Agents
0
Cytokines
0
Ethanol
3K9958V90M
mTOR protein, mouse
EC 2.7.1.1
Glycogen Synthase Kinase 3 beta
EC 2.7.11.1
Gsk3b protein, mouse
EC 2.7.11.1
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
Caspase 3
EC 3.4.22.-
Minocycline
FYY3R43WGO
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
25-35Subventions
Organisme : BLRD VA
ID : I01 BX001721
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA015407
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA017226
Pays : United States
Informations de copyright
Copyright © 2018 Elsevier Inc. All rights reserved.
Références
Mediators Inflamm. 2014;2014:629507
pubmed: 25525303
Addict Biol. 2017 Nov;22(6):1829-1841
pubmed: 27699959
J Neuroinflammation. 2017 Aug 4;14(1):156
pubmed: 28778220
J Neurosci. 1998 Apr 15;18(8):2933-43
pubmed: 9526010
Cell Mol Life Sci. 2014 Feb;71(4):683-97
pubmed: 24051980
Nat Rev Drug Discov. 2009 Aug;8(8):627-44
pubmed: 19644473
J Immunol. 2005 Nov 15;175(10):6893-9
pubmed: 16272348
Mediators Inflamm. 2015;2015:105828
pubmed: 26693205
J Biol Chem. 2003 Aug 29;278(35):33067-77
pubmed: 12796505
Alcohol Clin Exp Res. 2015 Mar;39(3):445-54
pubmed: 25703036
J Pharm Biomed Anal. 2012 Oct;69:209-22
pubmed: 22300909
Alcohol Clin Exp Res. 2016 Dec;40(12):2491-2498
pubmed: 27859429
Biochem Pharmacol. 2018 May;151:234-244
pubmed: 29288626
Endocrinology. 1999 Sep;140(9):3890-903
pubmed: 10465257
Mol Immunol. 2014 Jun;59(2):128-35
pubmed: 24603120
Neurobiol Dis. 2016 Jan;85:144-154
pubmed: 26459113
Nat Rev Neurosci. 2010 Aug;11(8):539-51
pubmed: 20648061
Am J Clin Dermatol. 2010;11(5):327-41
pubmed: 20642295
Brain Sci. 2016 Aug 16;6(3):
pubmed: 27537918
Front Neurol. 2011 Nov 21;2:68
pubmed: 22125548
Alcohol Clin Exp Res. 2011 Sep;35(9):1574-83
pubmed: 21599712
J Leukoc Biol. 2016 Nov;100(5):951-959
pubmed: 27462100
Neuropsychol Rev. 2011 Jun;21(2):73-80
pubmed: 21499711
Alcohol Clin Exp Res. 2016 Dec;40(12):2499-2505
pubmed: 27862011
J Leukoc Biol. 2005 Jul;78(1):135-43
pubmed: 15817702
J Matern Fetal Neonatal Med. 2011 Oct;24 Suppl 1:34-7
pubmed: 21942588
J Immunol. 2001 Jun 15;166(12):7527-33
pubmed: 11390507
Nat Med. 2000 Jul;6(7):797-801
pubmed: 10888929
Obstet Gynecol Clin North Am. 2014 Jun;41(2):177-89
pubmed: 24845483
Int Rev Neurobiol. 2014;118:81-103
pubmed: 25175862
J Neurochem. 2011 Jan;116(1):1-9
pubmed: 21044077
BMJ Open. 2018 Apr 27;8(4):e019907
pubmed: 29703853
Mol Cell. 2006 Oct 20;24(2):185-97
pubmed: 17052453
Exp Neurobiol. 2013 Jun;22(2):59-67
pubmed: 23833554
J Stud Alcohol Drugs. 2016 Mar;77(2):272-6
pubmed: 26997185
J Pediatr Hematol Oncol. 2015 May;37(4):245-51
pubmed: 25811750
Genes Dev. 2004 Aug 15;18(16):1926-45
pubmed: 15314020
Brain Res Dev Brain Res. 2002 Feb 28;133(2):115-26
pubmed: 11882342
Metab Brain Dis. 2013 Dec;28(4):667-76
pubmed: 23979425
FASEB J. 2010 Feb;24(2):337-45
pubmed: 19812374
Sci Rep. 2016 Feb 17;6:19670
pubmed: 26883396
J Mol Neurosci. 2014 Mar;52(3):366-77
pubmed: 24190281
Neurol Res. 2009 Mar;31(2):200-3
pubmed: 19298762
Neuropharmacology. 2018 Feb;129:84-99
pubmed: 29146504
J Neuroinflammation. 2016 Oct 4;13(1):259
pubmed: 27716270
Alcohol Res Health. 2001;25(3):159-67
pubmed: 11810953
Glia. 2002 Nov;40(2):164-74
pubmed: 12379904
Glia. 2016 Oct;64(10):1772-87
pubmed: 27219534
ScientificWorldJournal. 2008 Sep 21;8:873-82
pubmed: 18836653
Biochem Pharmacol. 2001 Aug 15;62(4):401-5
pubmed: 11448448
Neurotox Res. 2009 May;15(4):321-31
pubmed: 19384566
CNS Neurol Disord Drug Targets. 2012 Sep;11(6):705-21
pubmed: 22963440
Int Rev Neurobiol. 2014;118:41-80
pubmed: 25175861
J Pharm Pharmacol (Los Angel). 2013;1(1):001
pubmed: 25309941
Nat Clin Pract Rheumatol. 2008 Mar;4(3):136-44
pubmed: 18200008
Brain Behav Immun. 2017 Nov;66:210-220
pubmed: 28698116
J Affect Disord. 2018 Aug 1;235:96-104
pubmed: 29655081
Br J Pharmacol. 2012 Mar;165(5):1319-29
pubmed: 21955045
J Neuroinflammation. 2011 Jul 05;8:77
pubmed: 21729288
Cell Death Dis. 2013 Mar 07;4:e525
pubmed: 23470532
Neuron. 2014 Oct 22;84(2):275-91
pubmed: 25374355
Ann Transl Med. 2015 Jun;3(10):136
pubmed: 26207229
Sci Transl Med. 2016 Dec 7;8(368):368ra174
pubmed: 27928028
Neurochem Res. 2007 Apr-May;32(4-5):577-95
pubmed: 16944320
J Neurochem. 2004 Apr;89(1):197-203
pubmed: 15030404
Brain Behav Immun. 2016 Nov;58:130-141
pubmed: 27263429
Biochim Biophys Acta. 2013 Dec;1832(12):1913-21
pubmed: 23816568
Pharmacol Ther. 2014 Dec;144(3):321-37
pubmed: 25017304
Front Oncol. 2014 Apr 14;4:64
pubmed: 24782981
Curr Alzheimer Res. 2016;13(12):1319-1329
pubmed: 27539598
Free Radic Res. 2012 Aug;46(8):940-50
pubmed: 22583533
Stroke. 2007 Apr;38(4):1345-53
pubmed: 17332467
J Neurosci. 2012 Aug 22;32(34):11706-15
pubmed: 22915113
Alcohol. 2012 Feb;46(1):107-14
pubmed: 21889288
Glia. 2015 Oct;63(10):1694-713
pubmed: 25856413
J Neuroinflammation. 2017 Jan 25;14(1):22
pubmed: 28118842
Mol Pain. 2009 Jul 01;5:35
pubmed: 19570201
J Biol Chem. 2014 Jul 25;289(30):20615-29
pubmed: 24917666
Mol Neurobiol. 2009 Oct;40(2):108-21
pubmed: 19507062
J Neuroimmune Pharmacol. 2016 Mar;11(1):48-60
pubmed: 26139594
Brain Res Mol Brain Res. 1998 Jun 1;57(1):1-9
pubmed: 9630473
Curr Med Chem. 2007;14(11):1189-97
pubmed: 17504139
Metab Brain Dis. 2015 Apr;30(2):473-82
pubmed: 24833553
Glia. 2016 Oct;64(10):1788-94
pubmed: 27246804
Nat Cell Biol. 2004 Oct;6(10):931-40
pubmed: 15448698
Pharmacol Res. 2015 Jul;97:16-26
pubmed: 25829335
Stroke. 2001 May;32(5):1208-15
pubmed: 11340235
Neuropharmacology. 2017 Aug 1;122:56-73
pubmed: 28159648
Early Hum Dev. 2013 Jun;89 Suppl 1:S40-3
pubmed: 23809349
Eur J Pharmacol. 1987 Oct 27;142(3):489-90
pubmed: 2448149
Dokl Biochem Biophys. 2013 Jul-Aug;451:212-4
pubmed: 23975404
Lab Invest. 2007 Jun;87(6):613-24
pubmed: 17384665
Biochim Biophys Acta Mol Basis Dis. 2017 Nov;1863(11):2746-2761
pubmed: 28778590
Annu Rev Pharmacol Toxicol. 2012;52:111-33
pubmed: 21854227
Int J Mol Med. 2017 Jun;39(6):1338-1346
pubmed: 28440493
Am J Obstet Gynecol. 1999 Jan;180(1 Pt 1):1-7
pubmed: 9914568
Neuropharmacology. 2014 Apr;79:298-306
pubmed: 24262633
J Neurosci. 2000 Aug 1;20(15):5775-81
pubmed: 10908618
Biochim Biophys Acta. 2012 Oct;1823(10):1905-13
pubmed: 22771441
J Neurosci Res. 2009 Sep;87(12):2793-802
pubmed: 19382207
Exp Cell Res. 2008 Apr 1;314(6):1351-66
pubmed: 18261723
Brain Behav Immun. 2017 Feb;60:333-345
pubmed: 27647531
Sci Rep. 2017 Jul 10;7(1):4934
pubmed: 28694481