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Fumaric Acids Directly Influence Gene Expression of Neuroprotective Factors in Rodent Microglia

Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, 30559 Hannover, Germany
Center for Systems Neuroscience, University of Veterinary Medicine Hannover, 30559 Hannover, Germany
Department of Neurology, European Medical School, University Oldenburg, 26129 Oldenburg, Germany
Department of Neurology, University Clinic Essen, 45147 Essen, Germany
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(2), 325;
Received: 22 December 2018 / Revised: 10 January 2019 / Accepted: 11 January 2019 / Published: 15 January 2019
(This article belongs to the Special Issue New Molecular Mechanisms in Multiple Sclerosis)
Dimethylfumarate (DMF) has been approved the for treatment of relapsing-remitting multiple sclerosis. The mode of action of DMF and its assumed active primary metabolite monomethylfumarate (MMF) is still not fully understood, notably for brain resident cells. Therefore we investigated potential direct effects of DMF and MMF on microglia and indirect effects on oligodendrocytes. Primary rat microglia were differentiated into M1-like, M2-like and M0 phenotypes and treated in vitro with DMF or MMF. The gene expression of pro-inflammatory and anti-inflammatory factors such as growth factors (IGF-1), interleukins (IL-10, IL-1β), chemokines (CCl3, CXCL-10) as well as cytokines (TGF-1β, TNFα), iNOS, and the mannose receptor (MRC1) was examined by determining their transcription level with qPCR, and on the protein level by ELISA and FACS analysis. Furthermore, microglia function was determined by phagocytosis assays and indirect effects on oligodendroglial proliferation and differentiation. DMF treatment of M0 and M1-like polarized microglia demonstrated an upregulation of gene expression for IGF-1 and MRC1, but not on the protein level. While the phagocytic activity remained unchanged, DMF and MMF treated microglia supernatants led to an enhanced proliferation of oligodendrocyte precursor cells (OPC). These results suggest that DMF has anti-inflammatory effects on microglia which may result in enhanced proliferation of OPC. View Full-Text
Keywords: microglia; dimethylfumarate; monomethylfumarate; IGF-1 microglia; dimethylfumarate; monomethylfumarate; IGF-1
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MDPI and ACS Style

Kronenberg, J.; Pars, K.; Brieskorn, M.; Prajeeth, C.K.; Heckers, S.; Schwenkenbecher, P.; Skripuletz, T.; Pul, R.; Pavlou, A.; Stangel, M. Fumaric Acids Directly Influence Gene Expression of Neuroprotective Factors in Rodent Microglia. Int. J. Mol. Sci. 2019, 20, 325.

AMA Style

Kronenberg J, Pars K, Brieskorn M, Prajeeth CK, Heckers S, Schwenkenbecher P, Skripuletz T, Pul R, Pavlou A, Stangel M. Fumaric Acids Directly Influence Gene Expression of Neuroprotective Factors in Rodent Microglia. International Journal of Molecular Sciences. 2019; 20(2):325.

Chicago/Turabian Style

Kronenberg, Jessica, Kaweh Pars, Marina Brieskorn, Chittappen K. Prajeeth, Sandra Heckers, Philipp Schwenkenbecher, Thomas Skripuletz, Refik Pul, Andreas Pavlou, and Martin Stangel. 2019. "Fumaric Acids Directly Influence Gene Expression of Neuroprotective Factors in Rodent Microglia" International Journal of Molecular Sciences 20, no. 2: 325.

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