Testosterone Differentially Affects T Cells and Neurons in Murine and Human Models of Neuroinflammation and Neurodegeneration
2017
The high female-to-male sex ratio of multiple sclerosis (MS) prevalence has continuously confounded researchers, especially in light of male patients' accelerated disease course at later stages of MS. Although multiple studies have concentrated on estrogenic mechanisms of disease modulation, fairly little attention has been paid to androgenic effects in a female system, and even fewer studies have attempted to dissociate hormonal effects on the neurodegenerative and neuroinflammatory processes of MS. Herein, we demonstrate the differential effects of hormone treatment on the acute inflammatory and chronic neurodegenerative phases of murine
experimental autoimmune encephalomyelitis. Although s.c. treatment with testosterone and
aromatase inhibitorapplied beginning on the day of immunization ameliorated initial course of disease, similar treatment administered therapeutically
exacerbatedchronic disease course. Spinal cord analyses of axonal densities reflected the clinical scores of the chronic phase. In vitro , testosterone treatment not only decreased Th1 and Th17 differentiation in an
aromatase-independent fashion, but also
exacerbatedcell death in
induced pluripotent stem cell–derived primary human neurons under oxidative stress conditions in an
aromatase inhibitor–dependent manner. Thus, through the alleviation of inflammatory processes and the
exacerbationof neurodegenerative processes, androgens may contribute to the epidemiologic sex differentials observed in MS prevalence and course.
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