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Updated: Jun 22, 2026
Modeling Multiple Sclerosis in the Two Sexes: MOG35-55-Induced Experimental Autoimmune Encephalomyelitis
Published on: October 13, 2023
Protective effects of progesterone administration on axonal pathology in mice with experimental autoimmune
Laura Garay1, Maria Claudia Gonzalez Deniselle, Maria Meyer
1Laboratory of Neuroendocrine Biochemistry, Instituto de Biologia y Medicina Experimental, Buenos Aires, Argentina.
Abstract:
Experimental autoimmune encephalomyelitis (EAE), an induced model of Multiple Sclerosis presents spinal cord demyelination, axonal pathology and neuronal dysfunction. Previous work has shown that progesterone attenuated the clinical severity, demyelination and neuronal dysfunction of EAE mice (Garay et al., J. Steroid Biochem. Mol. Biol., 2008). Here we studied if progesterone also prevented axonal damage, a main cause of neurological disability. To this end, some axonal parameters were compared in EAE mice pretreated with progesterone a week before immunization with MOG(40-54) and in a group of steroid-free EAE mice. On day 16th after EAE induction, we determined in both groups and in control mice: a) axonal density in semithin sections of the spinal cord ventral funiculus; b) appearance of amyloid precursor protein (APP) immunopositive spheroids as an index of damaged axons; c) levels of the growth associated protein GAP43 mRNA and immunopositive cell bodies, as an index of aberrant axonal sprouting. Steroid-naive EAE mice showed decreased axonal density, shrunken axons, abundance of irregular vesicular structures, degenerating APP+ axons, increased expression of GAP43 mRNA and immunoreactive protein in motoneurons. Instead, EAE mice receiving progesterone treatment showed increased axonal counts, high proportion of small diameter axons, reduced APP+ profiles, and decreased GAP43 expression. In conclusion, progesterone enhanced axonal density, decreased axonal damage and prevented GAP43 hyperexpression in the spinal cord of EAE mice. Thus, progesterone also exerts protective effects on the axonal pathology developing in EAE mice.
Insights
Progesterone treatment reduced axonal damage and improved axonal density in mice with experimental autoimmune encephalomyelitis (EAE), a model for Multiple Sclerosis. This suggests progesterone protects against neurological disability by preserving nerve fibers.
Area of Science:
- Neuroscience
- Immunology
- Endocrinology
Background:
- Experimental autoimmune encephalomyelitis (EAE) is a mouse model of Multiple Sclerosis (MS), characterized by demyelination, axonal pathology, and neuronal dysfunction.
- Previous research indicated progesterone mitigates clinical severity, demyelination, and neuronal dysfunction in EAE mice.
- Axonal damage is a primary contributor to neurological disability in MS and EAE.
Purpose of the Study:
- To investigate whether progesterone administration prevents axonal damage in EAE mice.
- To compare axonal parameters in progesterone-treated EAE mice versus steroid-naive EAE mice and control groups.
Main Methods:
- Mice were induced with EAE using MOG(40-54) peptide.
- Progesterone treatment was administered one week prior to EAE induction.
- Axonal density, amyloid precursor protein (APP) positive spheroids (indicating axonal damage), and growth-associated protein 43 (GAP43) mRNA/protein levels (indicating axonal sprouting) were assessed in spinal cord sections on day 16 post-induction.
Main Results:
- Steroid-naive EAE mice exhibited reduced axonal density, shrunken axons, degenerating APP+ axons, and increased GAP43 expression.
- Progesterone-treated EAE mice demonstrated increased axonal counts, a higher proportion of small-diameter axons, fewer APP+ profiles, and reduced GAP43 expression.
- Progesterone treatment significantly improved axonal integrity and reduced markers of axonal damage and aberrant sprouting in EAE mice.
Conclusions:
- Progesterone enhances axonal density and decreases axonal damage in the spinal cord of EAE mice.
- Progesterone prevents the hyperexpression of GAP43 in the spinal cord of EAE mice, suggesting a reduction in aberrant axonal sprouting.
- Progesterone exerts protective effects on axonal pathology in the EAE model, indicating potential therapeutic benefits for MS-related neurological disability.
