Attenuation of neuroinflammation reverses Adriamycin-induced cognitive impairments.
Animals
Antibiotics, Antineoplastic
/ toxicity
Cognitive Dysfunction
/ chemically induced
Doxorubicin
/ toxicity
Humans
Induced Pluripotent Stem Cells
/ transplantation
Inflammation
/ chemically induced
Inflammation Mediators
/ antagonists & inhibitors
Male
Mice
Mice, Inbred C57BL
Organic Chemicals
/ pharmacology
Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
/ antagonists & inhibitors
Adriamycin
Chemobrain
Chemotherapy
Cognitive dysfunction
Colony stimulating factor receptor 1
Doxorubicin
Extracellular vesicles
Induced pluripotent stem cells
Microglia
Neuroinflammation
Journal
Acta neuropathologica communications
ISSN: 2051-5960
Titre abrégé: Acta Neuropathol Commun
Pays: England
ID NLM: 101610673
Informations de publication
Date de publication:
21 11 2019
21 11 2019
Historique:
received:
12
09
2019
accepted:
29
10
2019
entrez:
23
11
2019
pubmed:
23
11
2019
medline:
26
9
2020
Statut:
epublish
Résumé
Numerous clinical studies have established the debilitating neurocognitive side effects of chemotherapy in the treatment of breast cancer, often referred as chemobrain. We hypothesize that cognitive impairments are associated with elevated microglial inflammation in the brain. Thus, either elimination of microglia or restoration of microglial function could ameliorate cognitive dysfunction. Using a rodent model of chronic Adriamycin (ADR) treatment, a commonly used breast cancer chemotherapy, we evaluated two strategies to ameliorate chemobrain: 1) microglia depletion using the colony stimulating factor-1 receptor (CSF1R) inhibitor PLX5622 and 2) human induced pluripotent stem cell-derived microglia (iMG)-derived extracellular vesicle (EV) treatment. In strategy 1 mice received ADR once weekly for 4 weeks and were then administered CSF1R inhibitor (PLX5622) starting 72 h post-ADR treatment. ADR-treated animals given a normal diet exhibited significant behavioral deficits and increased microglial activation 4-6 weeks later. PLX5622-treated mice exhibited no ADR-related cognitive deficits and near complete depletion of IBA-1 and CD68
Identifiants
pubmed: 31753024
doi: 10.1186/s40478-019-0838-8
pii: 10.1186/s40478-019-0838-8
pmc: PMC6868786
doi:
Substances chimiques
Antibiotics, Antineoplastic
0
Csf1r protein, mouse
0
Inflammation Mediators
0
Organic Chemicals
0
PLX5622
0
Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
0
Doxorubicin
80168379AG
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
186Subventions
Organisme : Institute for Clinical and Translational Sciences, University of California Irvine (US)
ID : KL2TR001416
Pays : International
Organisme : University of California Irvine School of Medicine (US)
ID : 19900
Pays : International
Références
Metab Brain Dis. 2008 Sep;23(3):325-33
pubmed: 18690526
Nat Rev Drug Discov. 2013 May;12(5):347-57
pubmed: 23584393
Neuroscientist. 2003 Feb;9(1):10-22
pubmed: 12580336
Adv Exp Med Biol. 2010;678:55-69
pubmed: 20738007
Int J Radiat Oncol Biol Phys. 1995 Oct 15;33(3):619-26
pubmed: 7558951
Nat Rev Cancer. 2007 Mar;7(3):192-201
pubmed: 17318212
Clin Cancer Res. 2012 Apr 1;18(7):1954-65
pubmed: 22338017
Neurochem Res. 2019 Apr;44(4):811-828
pubmed: 30628018
Behav Brain Res. 2017 Jan 1;316:215-224
pubmed: 27599618
Nat Neurosci. 2007 Nov;10(11):1387-94
pubmed: 17965659
J Control Release. 2015 Jun 10;207:18-30
pubmed: 25836593
Toxicol Mech Methods. 2019 Jul;29(6):457-466
pubmed: 31010378
Nat Cell Biol. 2001 Feb;3(2):150-7
pubmed: 11175747
Mol Neurobiol. 2019 Oct;56(10):7159-7172
pubmed: 30989632
Front Cell Neurosci. 2019 Apr 02;13:97
pubmed: 31001085
Aging Cell. 2018 Dec;17(6):e12832
pubmed: 30276955
J Immunother Cancer. 2017 Jul 18;5(1):53
pubmed: 28716061
Neurobiol Learn Mem. 2010 May;93(4):487-94
pubmed: 20109567
Nat Biotechnol. 2011 Apr;29(4):341-5
pubmed: 21423189
Neuron. 2014 Apr 16;82(2):380-97
pubmed: 24742461
Br J Pharmacol. 2006 Nov;149(5):490-7
pubmed: 17001303
Mol Neurodegener. 2018 Dec 22;13(1):67
pubmed: 30577865
Brain Behav Immun. 2017 Jan;59:313-321
pubmed: 27562421
J Neurosci. 2007 Mar 14;27(11):2948-57
pubmed: 17360918
Curr Protoc Cell Biol. 2006 Apr;Chapter 3:Unit 3.22
pubmed: 18228490
Neuron. 2017 Apr 19;94(2):278-293.e9
pubmed: 28426964
Brain Behav Immun. 2010 Feb;24(2):243-53
pubmed: 19825412
Front Mol Neurosci. 2016 Jun 03;9:42
pubmed: 27375429
Nat Commun. 2019 Aug 21;10(1):3758
pubmed: 31434879
Cancer Res. 2015 Feb 15;75(4):676-86
pubmed: 25687405
Neuropharmacology. 2015 May;92:98-107
pubmed: 25623966
Stem Cells Transl Med. 2015 Jan;4(1):74-83
pubmed: 25391646
J Neuroimmunol. 2006 May;174(1-2):133-46
pubmed: 16574247
Biochem Biophys Res Commun. 2019 Oct 1;517(4):642-647
pubmed: 31402119
Front Pharmacol. 2012 Mar 09;3:41
pubmed: 22408626
Cancer Invest. 2010 Jun;28(5):544-53
pubmed: 20014946
Neurosci Biobehav Rev. 2019 Jul;102:382-399
pubmed: 31063740
J Neurosci. 2011 Jul 20;31(29):10721-31
pubmed: 21775615
Brain. 2016 Apr;139(Pt 4):1265-81
pubmed: 26921617
Biochim Biophys Acta. 2010 Oct;1802(10):903-17
pubmed: 19835956
Eur J Pharmacol. 2000 Jul 7;399(2-3):117-21
pubmed: 10884510
J Neurosci. 2015 Jul 8;35(27):9977-89
pubmed: 26156998
Sci Rep. 2016 Aug 12;6:31545
pubmed: 27516055
Cancer Res. 2011 Jul 15;71(14):4834-45
pubmed: 21757460
Brain Behav Immun. 2018 Feb;68:34-43
pubmed: 28943292
Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17501-6
pubmed: 17088541
Proc Natl Acad Sci U S A. 2016 Apr 26;113(17):4836-41
pubmed: 27044087
Acta Neuropathol. 2019 Dec;138(6):987-1012
pubmed: 31363836
Bone Marrow Transplant. 1998 Jan;21(2):209-14
pubmed: 9489640
Hippocampus. 2006;16(3):296-304
pubmed: 16411241
Neurobiol Dis. 2006 Jul;23(1):127-39
pubmed: 16697651
Exp Neurol. 2019 Aug;318:32-41
pubmed: 31029597