Differential effects of sex steroid hormones on the chronic and acute phases of experimental autoimmune encephalomyelitis
Author(s): ,
M.G. Massa
Affiliations:
Neurology, Ruhr University Bochum, Bochum, Germany
,
C. David
Affiliations:
Neurology, Ruhr University Bochum, Bochum, Germany
,
J. Berg
Affiliations:
Neurology, Ruhr University Bochum, Bochum, Germany
,
Y. Mahmoudjanlou
Affiliations:
Neurology, Ruhr University Bochum, Bochum, Germany
,
R. Gold
Affiliations:
Neurology, Ruhr University Bochum, Bochum, Germany
A. Haghikia
Affiliations:
Neurology, Ruhr University Bochum, Bochum, Germany
ECTRIMS Online Library. Massa M. 10/08/15; 115669; 881
Megan Massa
Megan Massa
Contributions
Abstract
Abstract: P299

Type: Poster

Abstract Category: MS and gender

The relationship between sex and multiple sclerosis (MS) has long been of interest. Though MS is traditionally viewed as a primarily autoinflammatory, demyelinating affliction of the central nervous system, recent research has demonstrated that neurodegenerative processes occur throughout disease course and contribute to patients' steady neurological decline. Indeed, like many autoimmune diseases, women incur an increased risk of development, particularly with regards to the relapsing-remitting disease course. However, this disparity reaches beyond mere incidence, with severity, disability, and even responsiveness to existing treatments being correlated with patient sex. This, coupled with recent studies demonstrating varying actions of hormonal treatments depending on timing to and type of stressor, gives reason to suggest that sex steroid hormones may differentially affect the inflammatory and neurodegenerative processes in MS. In an effort to dissociate the effects of sex steroid hormones on these processes, our study investigated the consequences of elevated androgens and estrogens during the various phases of EAE. Female mice aged 8-10 weeks were induced with an active myelin oligodendrocyte glycoprotein (MOG)-induced EAE. Mice were treated daily with testosterone (T) alone (considered the estrogenic group due to in vivo conversion of T to estradiol by aromatase) or T with the aromatase inhibitor fadrozole (FAD; androgenic group) at day of immunization (acute, inflammatory phase) or at day of first symptom onset (chronic, neurodegenerative phase). While androgens demonstrated a protective effect during the inflammatory stage, elevated estrogen levels conferred greater disease amelioration within the chronic phase, thus providing evidence within an animal model of the sex disparities seen in increased female incidence and male disability, respectively. These results contribute to a model which may partially account for sex differences found in MS disease incidence and subsequent disease course in the human population.

Disclosure:

Megan G. Massa: Nothing to disclose

Christina David: Nothing to disclose

Johannes Berg: Nothing to disclose

Ralf Gold: Nothing to disclose

Aiden Haghikia: Nothing to disclose
Abstract: P299

Type: Poster

Abstract Category: MS and gender

The relationship between sex and multiple sclerosis (MS) has long been of interest. Though MS is traditionally viewed as a primarily autoinflammatory, demyelinating affliction of the central nervous system, recent research has demonstrated that neurodegenerative processes occur throughout disease course and contribute to patients' steady neurological decline. Indeed, like many autoimmune diseases, women incur an increased risk of development, particularly with regards to the relapsing-remitting disease course. However, this disparity reaches beyond mere incidence, with severity, disability, and even responsiveness to existing treatments being correlated with patient sex. This, coupled with recent studies demonstrating varying actions of hormonal treatments depending on timing to and type of stressor, gives reason to suggest that sex steroid hormones may differentially affect the inflammatory and neurodegenerative processes in MS. In an effort to dissociate the effects of sex steroid hormones on these processes, our study investigated the consequences of elevated androgens and estrogens during the various phases of EAE. Female mice aged 8-10 weeks were induced with an active myelin oligodendrocyte glycoprotein (MOG)-induced EAE. Mice were treated daily with testosterone (T) alone (considered the estrogenic group due to in vivo conversion of T to estradiol by aromatase) or T with the aromatase inhibitor fadrozole (FAD; androgenic group) at day of immunization (acute, inflammatory phase) or at day of first symptom onset (chronic, neurodegenerative phase). While androgens demonstrated a protective effect during the inflammatory stage, elevated estrogen levels conferred greater disease amelioration within the chronic phase, thus providing evidence within an animal model of the sex disparities seen in increased female incidence and male disability, respectively. These results contribute to a model which may partially account for sex differences found in MS disease incidence and subsequent disease course in the human population.

Disclosure:

Megan G. Massa: Nothing to disclose

Christina David: Nothing to disclose

Johannes Berg: Nothing to disclose

Ralf Gold: Nothing to disclose

Aiden Haghikia: Nothing to disclose

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