Testosterone Differentially Affects T Cells and Neurons in Murine and Human Models of Neuroinflammation and Neurodegeneration
| Autor: | Stefanie Jörg, Barbara Gisevius, Megan G. Massa, Johannes Berg, Christina David, Ralf A. Linker, Ralf Gold, Aiden Haghikia, Sarah Hirschberg |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Encephalomyelitis Autoimmune Experimental Multiple Sclerosis medicine.drug_class medicine.disease_cause Pathology and Forensic Medicine 03 medical and health sciences Mice 0302 clinical medicine Internal medicine medicine Animals Humans Testosterone Aromatase Neuroinflammation Inflammation Neurons Aromatase inhibitor biology Fadrozole Aromatase Inhibitors Multiple sclerosis Neurodegeneration Experimental autoimmune encephalomyelitis Neurodegenerative Diseases Th1 Cells medicine.disease Axons Mice Inbred C57BL Disease Models Animal Oxidative Stress 030104 developmental biology Endocrinology Spinal Cord Immunology biology.protein Androgens Th17 Cells Female 030217 neurology & neurosurgery Oxidative stress |
| Zdroj: | The American journal of pathology. 187(7) |
| ISSN: | 1525-2191 |
| Popis: | 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 inhibitor applied beginning on the day of immunization ameliorated initial course of disease, similar treatment administered therapeutically exacerbated chronic 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 exacerbated cell 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 exacerbation of neurodegenerative processes, androgens may contribute to the epidemiologic sex differentials observed in MS prevalence and course. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|