Dimethyl Fumarate Reduces Microglia Functional Response to Tissue Damage and Favors Brain Iron Homeostasis.
dimethyl fumarate
ferritin
hippocampus
microglia
multiple sclerosis
purinergic receptors
Journal
Neuroscience
ISSN: 1873-7544
Titre abrégé: Neuroscience
Pays: United States
ID NLM: 7605074
Informations de publication
Date de publication:
15 07 2020
15 07 2020
Historique:
received:
09
04
2019
revised:
08
10
2019
accepted:
23
10
2019
pubmed:
19
11
2019
medline:
15
5
2021
entrez:
19
11
2019
Statut:
ppublish
Résumé
Dimethyl fumarate (DMF) is the only available approved drug for first line treatment of multiple sclerosis (MS), a lethal condition impairing central nervous system (CNS). To date, however, little is known of its mechanisms of action. Only recently, it has been suggested that DMF exerts neuroprotective effects acting as an immunomodulator and that it may alter the activation state of microglia cells, crucial in MS pathogenesis. However, DMF effects on microglia functions are still not well determined. Here, we examine the effects of DMF treatment on microglia functional activities, as phenotype, morphology, processes motility and rearrangement, migration, ATP response and iron uptake in mouse primary microglia culture and acute hippocampal slices. We found that DMF treatment reduces microglia motility, downregulating functional response to ATP, increases ferritin uptake and pushes microglia towards an anti-inflammatory phenotype, thus reducing its proinflammatory reactivity in response to tissue damage. These results highlight the effects of this compound on microglia functions and provide new insights on the mechanism of action of DMF in MS treatment.
Identifiants
pubmed: 31738884
pii: S0306-4522(19)30740-7
doi: 10.1016/j.neuroscience.2019.10.041
pii:
doi:
Substances chimiques
Immunosuppressive Agents
0
Pharmaceutical Preparations
0
Iron
E1UOL152H7
Dimethyl Fumarate
FO2303MNI2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
241-254Informations de copyright
Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Acknowledgements The authors have no conflict of interest to declare. The work was supported by the CrestOptics-IIT JointLab for Advanced Microscopy (to A.G. and S.D.A.), the MARBEL Life2020 grant (to S.D.A.), the SynaNet H2020 Program (to A.G.; B.B; S.D.A.; D.R.) and the “Progetti per Avvio alla Ricerca - Tipo 1” financed by Sapienza University of Rome (C.T.). The authors wish to thank PhD V. de Turris at the Center for Life Nano Science Imaging Facility, Istituto Italiano di Tecnologia, for support and technical advice on microscopy and image analysis. The authors wish to thank Dr. Cristina Limatola and Dr. Alberto Boffi for helpful discussions and assistance.