Contributions
Abstract: P858
Type: Poster
Abstract Category: Clinical aspects of MS - MS and gender
Multiple sclerosis (MS) is a presumably T cell-mediated inflammatory disease which is also characterized by early occurring neurodegenerative processes ultimately leading to progressive neurological deficits. In MS, there are apparent sex differences, which may depend upon sex steroid hormone levels. However, while previous research focused on estrogens, little is known about specific androgenic effects. Previous studies demonstrated that androgens may have the ability to affect inflammation and neurodegeneration depending on hormonal concentration, as well as timing and type of stressor. Furthermore, recent research has shown an effect of androgens on T cell differentiation, whose balance is disturbed in MS but crucial for an intact immune system.
In order to investigate putative differential effects of androgens on the inflammatory and neurodegenerative processes relevant in MS pathogenesis, timed hormonal treatments were administered to female C57BL/6J mice after MOG (myelin oligodendrocyte glycoprotein) EAE induction at the age of 8-10 weeks. Clinical disease course as well as histopathological analyses of inflammation and degeneration were investigated. Androgenic effects on T cell-differentiation were examined by extracting naïve T cells from female C57BL/6J mice and subjecting them to Th1- and Th17-polarizing conditions in the presence of androgens. Additionally, MS-patient derived neurons were cultured from induced pluripotent stem cells to perform apoptosis assays after hydrogen peroxide-mediated cell stress to test for testosterone mediated effects on neuronal survival.
Androgenic treatment led to disease amelioration when applied at immunization, but resulted in disease exacerbation when applied in the chronic phase of EAE. These phenotypes were reflected in the histological investigation. When added to Th1- and Th17-polarizing conditions, testosterone led to decreased levels of T cell differentiation (p < 0.01). Finally, MS-patient derived neurons were subjected to the stressor H2O2, adding testosterone after an incubation time to acquire implications with respect to neuronal death.
Our results provide evidence for a role of androgens in both T cell-modulation and neurodegeneration, thereby reflecting sex differences in MS epidemiology.
Disclosure: Christina David: nothing to disclose
Megan G. Massa: nothing to disclose
Stefanie Jörg: nothing to disclose
Johannes Berg: nothing to disclose
Barbara Gisevius: nothing to disclose
Sarah Hirschberg: nothing to disclose
Ralf A. Linker: holds an endowed professorship supported by the Novartis Foundation
Ralf Gold: has received limited travel grants from Bayer
Healthcare and Genzyme, and limited research grants from Genzyme.
Aiden Haghikia: has received limited travel grants from Bayer
Healthcare and Genzyme, and limited research grants from Genzyme.
Abstract: P858
Type: Poster
Abstract Category: Clinical aspects of MS - MS and gender
Multiple sclerosis (MS) is a presumably T cell-mediated inflammatory disease which is also characterized by early occurring neurodegenerative processes ultimately leading to progressive neurological deficits. In MS, there are apparent sex differences, which may depend upon sex steroid hormone levels. However, while previous research focused on estrogens, little is known about specific androgenic effects. Previous studies demonstrated that androgens may have the ability to affect inflammation and neurodegeneration depending on hormonal concentration, as well as timing and type of stressor. Furthermore, recent research has shown an effect of androgens on T cell differentiation, whose balance is disturbed in MS but crucial for an intact immune system.
In order to investigate putative differential effects of androgens on the inflammatory and neurodegenerative processes relevant in MS pathogenesis, timed hormonal treatments were administered to female C57BL/6J mice after MOG (myelin oligodendrocyte glycoprotein) EAE induction at the age of 8-10 weeks. Clinical disease course as well as histopathological analyses of inflammation and degeneration were investigated. Androgenic effects on T cell-differentiation were examined by extracting naïve T cells from female C57BL/6J mice and subjecting them to Th1- and Th17-polarizing conditions in the presence of androgens. Additionally, MS-patient derived neurons were cultured from induced pluripotent stem cells to perform apoptosis assays after hydrogen peroxide-mediated cell stress to test for testosterone mediated effects on neuronal survival.
Androgenic treatment led to disease amelioration when applied at immunization, but resulted in disease exacerbation when applied in the chronic phase of EAE. These phenotypes were reflected in the histological investigation. When added to Th1- and Th17-polarizing conditions, testosterone led to decreased levels of T cell differentiation (p < 0.01). Finally, MS-patient derived neurons were subjected to the stressor H2O2, adding testosterone after an incubation time to acquire implications with respect to neuronal death.
Our results provide evidence for a role of androgens in both T cell-modulation and neurodegeneration, thereby reflecting sex differences in MS epidemiology.
Disclosure: Christina David: nothing to disclose
Megan G. Massa: nothing to disclose
Stefanie Jörg: nothing to disclose
Johannes Berg: nothing to disclose
Barbara Gisevius: nothing to disclose
Sarah Hirschberg: nothing to disclose
Ralf A. Linker: holds an endowed professorship supported by the Novartis Foundation
Ralf Gold: has received limited travel grants from Bayer
Healthcare and Genzyme, and limited research grants from Genzyme.
Aiden Haghikia: has received limited travel grants from Bayer
Healthcare and Genzyme, and limited research grants from Genzyme.