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Updated: May 18, 2026
Modeling Multiple Sclerosis in the Two Sexes: MOG35-55-Induced Experimental Autoimmune Encephalomyelitis
Published on: October 13, 2023
Progesterone down-regulates spinal cord inflammatory mediators and increases myelination in experimental autoimmune
L I Garay1, M C González Deniselle, M E Brocca
1Laboratory of Neuroendocrine Biochemistry, Instituto de Biologia y Medicina Experimental-CONICET, Obligado 2490, 1428 Buenos Aires, Argentina. laurainesgaray@gmaill.com
Abstract:
In mice with experimental autoimmune encephalomyelitis (EAE) pretreatment with progesterone improves clinical signs and decreases the loss of myelin basic protein (MBP) and proteolipid protein (PLP) measured by immunohistochemistry and in situ hybridization. Presently, we analyzed if progesterone effects in the spinal cord of EAE mice involved the decreased transcription of local inflammatory mediators and the increased transcription of myelin proteins and myelin transcription factors. C57Bl/6 female mice were divided into controls, EAE and EAE receiving progesterone (100mg implant) 7 days before EAE induction. Tissues were collected on day 17 post-immunization. Real time PCR technology demonstrated that progesterone blocked the EAE-induced increase of the proinflammatory mediators tumor necrosis factor alpha (TNFα) and its receptor TNFR1, the microglial marker CD11b and toll-like receptor 4 (TLR4) mRNAs, and increased mRNA expression of PLP and MBP, the myelin transcription factors NKx2.2 and Olig1 and enhanced CC1+oligodendrocyte density respect of untreated EAE mice. Immunocytochemistry demonstrated decreased Iba1+microglial cells. Confocal microscopy demonstrated that TNFα colocalized with glial-fibrillary acidic protein+astrocytes and OX-42+microglial cells. Therefore, progesterone treatment improved the clinical signs of EAE, decreased inflammatory glial reactivity and increased myelination. Data suggest that progesterone neuroprotection involves the modulation of transcriptional events in the spinal cord of EAE mice.
Insights
Progesterone treatment in mice with experimental autoimmune encephalomyelitis (EAE) reduced inflammation and improved myelin repair. This neuroprotection involved regulating gene expression in the spinal cord, enhancing recovery from EAE.
Area of Science:
- Neuroscience
- Immunology
- Endocrinology
Background:
- Experimental autoimmune encephalomyelitis (EAE) is an animal model for multiple sclerosis.
- Progesterone has shown potential neuroprotective effects in EAE models.
- The precise mechanisms of progesterone's action in EAE remain under investigation.
Purpose of the Study:
- To investigate the transcriptional changes in the spinal cord of EAE mice treated with progesterone.
- To determine if progesterone modulates inflammatory mediators and myelin protein expression.
- To elucidate the role of progesterone in glial cell activity and myelination.
Main Methods:
- EAE was induced in C57Bl/6 female mice, with one group receiving progesterone pretreatment.
- Real-time PCR was used to quantify mRNA levels of inflammatory mediators and myelin proteins.
- Immunocytochemistry and confocal microscopy assessed glial cell markers and protein localization.
Main Results:
- Progesterone significantly reduced the EAE-induced increase in pro-inflammatory mediators like tumor necrosis factor alpha (TNFα) and toll-like receptor 4 (TLR4).
- Treatment increased the mRNA expression of myelin proteins (MBP, PLP) and myelin transcription factors (NKx2.2, Olig1).
- Progesterone decreased microglial activation (Iba1+) and enhanced oligodendrocyte density (CC1+), indicating reduced inflammation and improved myelination.
Conclusions:
- Progesterone treatment ameliorates clinical signs of EAE by reducing spinal cord inflammation and glial reactivity.
- Progesterone enhances myelination through the increased transcription of myelin proteins and associated factors.
- The neuroprotective effects of progesterone in EAE are mediated by the modulation of transcriptional events.
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