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.

Dimethyl fumarate reduces microglia functional response to tissue damage and favors brain iron homeostasis / Pagani, Francesca; Testi, Claudia; Grimaldi, Alfonso; Corsi, Giorgio; Cortese, Barbara; Basilico, Bernadette; Baiocco, Paola; De Panfilis, Simone; Ragozzino, Davide; Di Angelantonio, Silvia. - In: NEUROSCIENCE. - ISSN 0306-4522. - (2019), pp. 241-254. [10.1016/j.neuroscience.2019.10.041]

Dimethyl fumarate reduces microglia functional response to tissue damage and favors brain iron homeostasis

Pagani, Francesca
Investigation
;
Testi, Claudia
Investigation
;
Grimaldi, Alfonso
Investigation
;
CORSI, GIORGIO
Investigation
;
Basilico, Bernadette
Data Curation
;
Baiocco, Paola
Investigation
;
De Panfilis, Simone
Data Curation
;
Ragozzino, Davide
Writing – Original Draft Preparation
;
Di Angelantonio, Silvia
Conceptualization
2019

Abstract

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.
2019
dimethyl fumarate; ferritin; hippocampus; microglia; multiple sclerosis; purinergic receptors
01 Pubblicazione su rivista::01a Articolo in rivista
Dimethyl fumarate reduces microglia functional response to tissue damage and favors brain iron homeostasis / Pagani, Francesca; Testi, Claudia; Grimaldi, Alfonso; Corsi, Giorgio; Cortese, Barbara; Basilico, Bernadette; Baiocco, Paola; De Panfilis, Simone; Ragozzino, Davide; Di Angelantonio, Silvia. - In: NEUROSCIENCE. - ISSN 0306-4522. - (2019), pp. 241-254. [10.1016/j.neuroscience.2019.10.041]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1335927
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