Microglia lacking a peroxisomal β-oxidation enzyme chronically alter their inflammatory profile without evoking neuronal and behavioral deficits.
Animals
Animals, Newborn
Brain
/ drug effects
CX3C Chemokine Receptor 1
/ metabolism
Calcium-Binding Proteins
/ metabolism
Cell Proliferation
/ drug effects
Cells, Cultured
Disease Models, Animal
Evoked Potentials, Auditory, Brain Stem
/ drug effects
Exploratory Behavior
/ drug effects
Facial Nerve Diseases
/ complications
Functional Laterality
Gene Expression Regulation
/ drug effects
Hand Strength
/ physiology
Inflammation
/ chemically induced
Interleukin-4
/ administration & dosage
Lipopolysaccharides
/ toxicity
Mice
Mice, Transgenic
Microfilament Proteins
/ metabolism
Microglia
/ drug effects
Peroxisomal Multifunctional Protein-2
/ deficiency
Behavior
Conditional mouse model
Facial nerve axotomy
Immune response
Microglia
Peroxisomes
β-Oxidation
Journal
Journal of neuroinflammation
ISSN: 1742-2094
Titre abrégé: J Neuroinflammation
Pays: England
ID NLM: 101222974
Informations de publication
Date de publication:
13 Mar 2019
13 Mar 2019
Historique:
received:
11
12
2018
accepted:
24
02
2019
entrez:
15
3
2019
pubmed:
15
3
2019
medline:
16
7
2019
Statut:
epublish
Résumé
Microglia play a central role in most neurological disorders, but the impact of microgliosis on brain environment and clinical functions is not fully understood. Mice lacking multifunctional protein-2 (MFP2), a pivotal enzyme in peroxisomal β-oxidation, develop a fatal disorder characterized by motor problems similar to the milder form of MFP2 deficiency in humans. The hallmark of disease in mice is the chronic proliferation of microglia in the brain, but molecular pathomechanisms that drive rapid clinical deterioration in human and mice remain unknown. In the present study, we identified the effects of specific deletion of MFP2 from microglia in the brain on immune responses, neuronal functioning, and behavior. We created a novel Cx3cr1-Mfp2 We found that Mfp2 Our data demonstrate that MFP2 deficiency in microglia causes intrinsic dysregulation of their inflammatory profile, which is not harmful to neuronal function, motor function, and cognition in mice during their first year of life.
Sections du résumé
BACKGROUND
BACKGROUND
Microglia play a central role in most neurological disorders, but the impact of microgliosis on brain environment and clinical functions is not fully understood. Mice lacking multifunctional protein-2 (MFP2), a pivotal enzyme in peroxisomal β-oxidation, develop a fatal disorder characterized by motor problems similar to the milder form of MFP2 deficiency in humans. The hallmark of disease in mice is the chronic proliferation of microglia in the brain, but molecular pathomechanisms that drive rapid clinical deterioration in human and mice remain unknown. In the present study, we identified the effects of specific deletion of MFP2 from microglia in the brain on immune responses, neuronal functioning, and behavior.
METHODS
METHODS
We created a novel Cx3cr1-Mfp2
RESULTS
RESULTS
We found that Mfp2
CONCLUSION
CONCLUSIONS
Our data demonstrate that MFP2 deficiency in microglia causes intrinsic dysregulation of their inflammatory profile, which is not harmful to neuronal function, motor function, and cognition in mice during their first year of life.
Identifiants
pubmed: 30866963
doi: 10.1186/s12974-019-1442-3
pii: 10.1186/s12974-019-1442-3
pmc: PMC6417251
doi:
Substances chimiques
Aif1 protein, mouse
0
CX3C Chemokine Receptor 1
0
Calcium-Binding Proteins
0
Cx3cr1 protein, mouse
0
Lipopolysaccharides
0
Microfilament Proteins
0
Interleukin-4
207137-56-2
Hsd17b4 protein, mouse
EC 1.1.1.119
Peroxisomal Multifunctional Protein-2
EC 4.2.1.107
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
61Subventions
Organisme : Vlaamse regering
ID : G.0675.12
Organisme : Vlaamse regering
ID : G.0A15.13
Organisme : Onderzoeksraad, KU Leuven
ID : OT12/78
Références
J Biol Chem. 2000 May 26;275(21):16329-36
pubmed: 10748062
Methods. 2001 Dec;25(4):402-8
pubmed: 11846609
Neuron. 2002 Aug 1;35(3):419-32
pubmed: 12165466
Brain Res Brain Res Rev. 2004 Mar;44(2-3):154-78
pubmed: 15003391
Nat Neurosci. 2005 Jun;8(6):752-8
pubmed: 15895084
J Neurosci. 2005 Jul 13;25(28):6539-49
pubmed: 16014715
Ann Neurol. 2006 Jan;59(1):92-104
pubmed: 16278854
Am J Pathol. 2006 Apr;168(4):1321-34
pubmed: 16565505
Nat Neurosci. 2006 Jul;9(7):917-24
pubmed: 16732273
Biochim Biophys Acta. 2006 Sep;1761(9):973-94
pubmed: 16766224
Neurobiol Aging. 2008 Nov;29(11):1754-62
pubmed: 17544173
J Neurosci. 2008 Apr 9;28(15):4015-27
pubmed: 18400901
Brain. 2009 Feb;132(Pt 2):288-95
pubmed: 18567623
J Leukoc Biol. 2010 Sep;88(3):495-505
pubmed: 20504948
J Lipid Res. 2010 Oct;51(10):2863-95
pubmed: 20558530
Prog Neurobiol. 2010 Nov;92(3):293-315
pubmed: 20609379
Am J Hum Genet. 2010 Aug 13;87(2):282-8
pubmed: 20673864
Neuroradiology. 2010 Dec;52(12):1163-6
pubmed: 20848092
Neuroscience. 1990;39(1):151-70
pubmed: 2089275
Am J Pathol. 2011 Oct;179(4):2016-27
pubmed: 21872563
Nat Rev Immunol. 2011 Oct 25;11(11):775-87
pubmed: 22025055
J Neuroinflammation. 2012 Mar 29;9:61
pubmed: 22458306
Nat Immunol. 2012 Jun 24;13(8):753-60
pubmed: 22729249
Nat Immunol. 2012 Jul 19;13(8):717-9
pubmed: 22814343
Immunity. 2012 Dec 14;37(6):1050-1060
pubmed: 23177320
Dev Cell. 2012 Dec 11;23(6):1189-202
pubmed: 23201120
Immunity. 2013 Jan 24;38(1):79-91
pubmed: 23273845
J Neurosci. 2013 Feb 6;33(6):2481-93
pubmed: 23392676
Front Cell Neurosci. 2013 Mar 18;7:26
pubmed: 23507975
Neuropharmacology. 2014 Jan;76 Pt C:719-28
pubmed: 23688926
Neurobiol Dis. 2013 Oct;58:258-69
pubmed: 23777740
Biochimie. 2014 Mar;98:119-26
pubmed: 23969159
Neurology. 2014 Mar 18;82(11):963-8
pubmed: 24553428
BMC Med Genet. 2014 Mar 06;15:30
pubmed: 24602372
Cell. 2014 Jul 3;158(1):15-24
pubmed: 24995975
J Neurosci. 2014 Sep 3;34(36):11929-47
pubmed: 25186741
J Neuroinflammation. 2014 Dec 31;11:211
pubmed: 25551794
Brain. 2015 May;138(Pt 5):1138-59
pubmed: 25823474
Glia. 2015 Sep;63(9):1606-20
pubmed: 25846981
Immunity. 2016 Mar 15;44(3):505-515
pubmed: 26982357
Mol Cell Neurosci. 2017 Apr;80:123-133
pubmed: 28286294
Nat Neurosci. 2017 Jun;20(6):793-803
pubmed: 28414331
Hum Mol Genet. 2017 Aug 1;26(15):2850-2863
pubmed: 28453791
Immunity. 2017 Sep 19;47(3):566-581.e9
pubmed: 28930663
Sci Rep. 2018 Jan 10;8(1):256
pubmed: 29321503
Brain Pathol. 2018 Sep;28(5):631-643
pubmed: 29341299
Nat Immunol. 2018 Jun;19(6):636-644
pubmed: 29777220
Front Cell Neurosci. 2018 May 23;12:136
pubmed: 29892213
J Leukoc Biol. 2018 Nov;104(5):931-951
pubmed: 30066957
Biochim Biophys Acta Mol Cell Biol Lipids. 2019 Apr;1864(4):567-576
pubmed: 30312667