PMID- 35203379
OWN - NLM
STAT- MEDLINE
DCOM- 20220408
LR  - 20220408
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 11
IP  - 4
DP  - 2022 Feb 18
TI  - The Modulatory Effects of DMF on Microglia in Aged Mice Are Sex-Specific.
LID - 10.3390/cells11040729 [doi]
LID - 729
AB  - There is a striking sex-related difference in the prevalence of many 
      neurodegenerative diseases, highlighting the need to consider whether treatments 
      may exert sex-specific effects. A change in microglial activation state is a 
      common feature of several neurodegenerative diseases and is considered to be a 
      key factor in driving the inflammation that characterizes these conditions. Among 
      the changes that have been described is a switch in microglial metabolism towards 
      glycolysis which is associated with production of inflammatory mediators and 
      reduced function. Marked sex-related differences in microglial number, phenotype 
      and function have been described in late embryonic and early postnatal life in 
      rodents and some reports suggest that sexual dimorphism extends into adulthood 
      and age and, in models of Alzheimer's disease, the changes are more profound in 
      microglia from female, compared with male, mice. Dimethyl fumarate (DMF) is a 
      fumaric acid ester used in the treatment of psoriasis and relapsing remitting 
      multiple sclerosis and, while its mechanism of action is unclear, it possesses 
      anti-inflammatory and anti-oxidant properties and also impacts on cell 
      metabolism. Here we treated 16-18-month-old female and male mice with DMF for 1 
      month and assessed its effect on microglia. The evidence indicates that it 
      exerted sex-specific effects on microglial morphology and metabolism, reducing 
      glycolysis only in microglia from female mice. The data suggest that this may 
      result from its ability to inactivate glyceraldehyde-3-phosphate dehydrogenase 
      (GAPDH).
FAU - Mela, Virginia
AU  - Mela V
AUID- ORCID: 0000-0001-7702-0972
AD  - Department of Medicine and Dermatology, Faculty of Medicine, University of 
      Malaga, 29010 Malaga, Spain.
FAU - Sayd Gaban, Aline
AU  - Sayd Gaban A
AD  - Trinity College Institute of Neuroscience, Trinity College Dublin, D02 DK07 
      Dublin, Ireland.
FAU - O'Neill, Eoin
AU  - O'Neill E
AUID- ORCID: 0000-0002-2472-7795
AD  - Trinity College Institute of Neuroscience, Trinity College Dublin, D02 DK07 
      Dublin, Ireland.
FAU - Bechet, Sibylle
AU  - Bechet S
AD  - Trinity College Institute of Neuroscience, Trinity College Dublin, D02 DK07 
      Dublin, Ireland.
FAU - Walsh, Aife
AU  - Walsh A
AD  - Trinity College Institute of Neuroscience, Trinity College Dublin, D02 DK07 
      Dublin, Ireland.
FAU - Lynch, Marina A
AU  - Lynch MA
AUID- ORCID: 0000-0002-4631-0499
AD  - Trinity College Institute of Neuroscience, Trinity College Dublin, D02 DK07 
      Dublin, Ireland.
LA  - eng
GR  - 15/iA/3052/SFI_/Science Foundation Ireland/Ireland
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220218
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - 0 (Inflammation Mediators)
RN  - FO2303MNI2 (Dimethyl Fumarate)
SB  - IM
MH  - Animals
MH  - *Dimethyl Fumarate/metabolism
MH  - Female
MH  - Inflammation/metabolism
MH  - Inflammation Mediators/metabolism
MH  - Male
MH  - Mice
MH  - Microglia/metabolism
MH  - *Multiple Sclerosis, Relapsing-Remitting/metabolism
PMC - PMC8870377
OTO - NOTNLM
OT  - age
OT  - dimethyl fumarate
OT  - inflammation
OT  - metabolism
OT  - microglia
OT  - sexual dimorphism
COIS- The authors declare no conflict of interest.
EDAT- 2022/02/26 06:00
MHDA- 2022/04/09 06:00
PMCR- 2022/02/18
CRDT- 2022/02/25 01:01
PHST- 2022/01/12 00:00 [received]
PHST- 2022/02/08 00:00 [revised]
PHST- 2022/02/16 00:00 [accepted]
PHST- 2022/02/25 01:01 [entrez]
PHST- 2022/02/26 06:00 [pubmed]
PHST- 2022/04/09 06:00 [medline]
PHST- 2022/02/18 00:00 [pmc-release]
AID - cells11040729 [pii]
AID - cells-11-00729 [pii]
AID - 10.3390/cells11040729 [doi]
PST - epublish
SO  - Cells. 2022 Feb 18;11(4):729. doi: 10.3390/cells11040729.