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Sex hormones in experimental autoimmune encephalomyelitis: implications for multiple sclerosis
1Department of Neurology, University of California, Los Angeles 90095, USA. rvoskuhl@ucla.edu
Summary
Female mice show higher susceptibility to multiple sclerosis (MS) than males. This study in an experimental autoimmune encephalomyelitis (EAE) model reveals testosterone protects males, while estriol reduces disease activity in late pregnancy.
Area of Science:
- Neuroimmunology
- Endocrinology
- Animal Models of Disease
Background:
- Females exhibit higher susceptibility to multiple sclerosis (MS) compared to males.
- MS disease activity notably decreases during late pregnancy.
- These phenomena are mirrored in the experimental autoimmune encephalomyelitis (EAE) mouse model.
Purpose of the Study:
- To investigate the role of sex hormones in sex-based differences in MS susceptibility.
- To examine the influence of sex hormones on disease activity during pregnancy in an EAE model.
- To elucidate the hormonal mechanisms underlying EAE pathogenesis and its modulation by pregnancy.
Main Methods:
- Utilizing the experimental autoimmune encephalomyelitis (EAE) model in SJL mice.
- Employing castration and exogenous hormone administration to manipulate sex hormone levels.
- Analyzing the impact of these hormonal interventions on EAE disease incidence and severity.
Main Results:
- Male mice exhibit reduced EAE susceptibility due to a protective effect of testosterone.
- Elevated levels of estriol during late pregnancy contribute to decreased EAE disease severity.
- Hormonal modulation via castration and hormone treatment clarifies sex-specific EAE responses.
Conclusions:
- Testosterone plays a crucial role in conferring resistance to EAE in male mice.
- Estriol significantly mitigates EAE progression, particularly during the late stages of pregnancy.
- Sex hormones are key determinants of susceptibility and disease course in experimental autoimmune encephalomyelitis.