Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) By
Progesterone Therapy Induces an M1 to M2 Switch in Microglia Phenotype and Suppresses Nlrp3 Inflammasome in a Cuprizone-Induced Demyelination Mouse Model Publisher Pubmed



Aryanpour R1 ; Pasbakhsh P1 ; Zibara K2 ; Namjoo Z3 ; Beigi Boroujeni F1 ; Shahbeigi S1 ; Kashani IR1 ; Beyer C4 ; Zendehdel A4, 5
Authors
Show Affiliations
Authors Affiliations
  1. 1. Department of Anatomy, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. ER045, Laboratory of Stem Cells, DSST, Biology Department, Faculty of Sciences, Lebanese University, Beirut, Lebanon
  3. 3. Department of Anatomy, Faculty of Medicine, Faculty of Medicine, Iran University of Medical Science, Tehran, Iran
  4. 4. Institute of Neuroanatomy, RWTH Aachen University, Aachen, Germany
  5. 5. Giulan Neuroscience Research Center, Department of Anatomical Sciences, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran

Source: International Immunopharmacology Published:2017


Abstract

Demyelination of the central nervous system (CNS) has been associated to reactive microglia in neurodegenerative disorders, such as multiple sclerosis (MS). The M1 microglia phenotype plays a pro-inflammatory role while M2 is involved in anti-inflammatory processes in the brain. In this study, CPZ-induced demyelination mouse model was used to investigate the effect of progesterone (PRO) therapy on microglia activation and neuro-inflammation. Results showed that progesterone therapy (CPZ + PRO) decreased neurological behavioral deficits, as demonstrated by significantly decreased escape latencies, in comparison to CPZ mice. In addition, CPZ + PRO caused a significant reduction in the mRNA expression levels of M1-markers (iNOS, CD86, MHC-II and TNF-α) in the corpus callosum region, whereas the expression of M2-markers (Trem-2, CD206, Arg-1 and TGF-β) was significantly increased, in comparison to CPZ mice. Moreover, CPZ + PRO resulted in a significant decrease in the number of iNOS+ and Iba-1+/iNOS+ cells (M1), whereas TREM-2+ and Iba-1+/TREM-2+ cells (M2) significantly increased, in comparison to CPZ group. Furthermore, CPZ + PRO caused a significant decrease in mRNA and protein expression levels of NLRP3 and IL-18 (~ 2-fold), in comparison to the CPZ group. Finally, CPZ + PRO therapy was accompanied with reduced levels of demyelination, compared to CPZ, as confirmed by immunofluorescence to myelin basic protein (MBP) and Luxol Fast Blue (LFB) staining, as well as transmission electron microscopy (TEM) analysis. In summary, we reported for the first time that PRO therapy causes polarization of M2 microglia, attenuation of M1 phenotype, and suppression of NLRP3 inflammasome in a CPZ-induced demyelination model of MS. © 2017 Elsevier B.V.
Other Related Docs
10. The Role of Inflammasome Complex in Ischemia-Reperfusion Injury, Journal of Cellular Biochemistry (2023)
17. Neuroinflammation As a Potential Therapeutic Target in Neuroimmunological Diseases, Translational Neuroimmunology: Neuroinflammation: Volume 7 (2023)