Abstract
Background
Microglia play a major role in the development of brain inflammation after central nervous system injury. On the other hand, microglia also participate in the repair process. The dualistic role of these cells results from the fact that various states of their activation are associated with specific phenotypes. The M1 phenotype is responsible for the production of proinflammatory mediators, whereas the M2 microglia release anti-inflammatory and trophic factors and take part in immunosuppressive and neuroprotective processes. The histone deacetylase inhibitor sodium butyrate (SB) shows anti-inflammatory and neuroprotective effects in some animal models of brain injury. The aim of this study was to examine the effects of sodium butyrate on the proliferation and M1/M2 polarization of primary microglial cells after oxygen and glucose deprivation (OGD) in vitro.
Methods
Primary microglial cultures were prepared from 1-day-old rats, subjected to the OGD procedure and treated with SB (0.1 mM, 1 mM and 10 mM). The effect of OGD and SB on microglial proliferation was assessed by double immunofluorescence, and microglial phenotypes were evaluated by qPCR.
Results
The OGD procedure stimulated the proliferation of microglia after 24 h of culturing, and SB treatment reduced the division of these cells. This effect was inversely proportional to the SB concentration. The OGD procedure increased proinflammatory CD86 and IL1β gene expression and reduced the expression of the anti-inflammatory M2 markers arginase and CD200 in microglia.
Conclusions
SB can change the polarization of microglia after OGD from an unfavourable M1 to a beneficial M2 phenotype. Our results show that SB is a potential immunosuppressive agent that can modulate microglial activation stimulated by ischaemic-like conditions.
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Data availability
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
Abbreviations
- CNS:
-
Central nervous system
- DIV:
-
Day(s) in vitro
- GDNF:
-
Glial cell line-derived neurotrophic factor
- HATs:
-
Histone acetyl-transferases
- HDACs:
-
Histone deacetylases
- HDACis:
-
Histone deacetylase inhibitors
- HI:
-
Hypoxia–ischaemia
- IGF:
-
Insulin growth factor
- IL-10:
-
Interleukin 10
- IL-1β:
-
Interleukin 1β
- LPS:
-
Lipopolysaccharide
- MMPs:
-
Matrix metalloproteinases
- NO:
-
Nitric oxide,
- NOS:
-
Nitric oxide synthase
- OGD:
-
Oxygen and glucose deprivation
- PBS:
-
Phosphate-buffered saline buffer
- PFA:
-
Paraformaldehyde
- PLL:
-
Poly-L-lysine
- ROS:
-
Reactive oxygen species
- SAHA:
-
Vorinostat
- SB:
-
Sodium butyrate
- TGF β:
-
Transforming growth factor β
- TSA:
-
Trichostatin A
- VPA:
-
Valproic acid
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Acknowledgements
The confocal analysis of immunocytochemical staining was performed in the Laboratory of Advanced Microscopy Techniques, Mossakowski Medical Research Institute, Polish Academy of Sciences.
Funding
This work was supported by National Science Centre, Poland grant no 2017/27/B/NZ3/00582. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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KZ performed and analysed the data, prepared figures, and contributed to writing the manuscript, JG performed some in vitro experiments, JS contributed to writing the manuscript, MZ-N designed experiments, analysed and interpreted the data, and was a major contributor in writing the manuscript. All authors read and approved the final manuscript.
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Ziabska, K., Gargas, J., Sypecka, J. et al. The impact of the histone deacetylase inhibitor sodium butyrate on microglial polarization after oxygen and glucose deprivation. Pharmacol. Rep 74, 909–919 (2022). https://doi.org/10.1007/s43440-022-00384-x
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DOI: https://doi.org/10.1007/s43440-022-00384-x