Presenter's Name(s)

Grace Kathryn VoorheesFollow

Primary Faculty Mentor Name

Dimitry Krementsov

Project Collaborators

Mahalia McGill; "Bristy" Sabikunnahar

Secondary Mentor NetID

amorielli

Secondary Mentor Name

Anthony Morielli

Status

Graduate

Student College

Larner College of Medicine

Program/Major

Pharmacology

Primary Research Category

Health Sciences

Secondary Research Category

Biological Sciences

Presentation Title

Understanding the Role of Androgen Receptor Signaling in Modulating p38 MAPK in EAE

Time

9:00 AM

Location

Silver Maple Ballroom - Biological Sciences

Abstract

Multiple Sclerosis (MS) is an inflammatory autoimmune disease of the central nervous system (CNS), characterized by axonal demyelination and multifocal inflammation. Like many autoimmune diseases, MS is a sexually dimorphic disease, being 3-4 times more common in females than in males. p38 MAP kinase (MAPK) has an integral role in modulating inflammatory processes in autoimmunity. Conditionally knocking p38 MAPK out of myeloid cells in B6 mice shows a sexually dimorphic response to disease, which can be reversed by removal of sex hormones. This suggests that sex hormones may modulate the role of p38 MAPK. It is hypothesized that pathogenic inflammation in the animal model of MS, experimental autoimmune encephalomyelitis (EAE), is p38-independent in the presence of androgens and p38-dependent in the presence of estrogens. We tested this hypothesis by conditional or global genetic ablation of the primary mediator of androgenic effects, the androgen receptor (AR). Both in vivo and in vitro techniques were used to assess how AR signaling impacts the role of p38 in EAE pathogenesis and macrophage function. In vivo results from p38WT global AR knockout mice show no direct impact of AR signaling on EAE pathogenesis. In vitro results show no effect of androgens on pharmacologic p38 inhibition in the immortalized cell line RAW 264.7 macrophages. EAE results from p38 conditional knockout and AR knockout mice are pending.

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Understanding the Role of Androgen Receptor Signaling in Modulating p38 MAPK in EAE

Multiple Sclerosis (MS) is an inflammatory autoimmune disease of the central nervous system (CNS), characterized by axonal demyelination and multifocal inflammation. Like many autoimmune diseases, MS is a sexually dimorphic disease, being 3-4 times more common in females than in males. p38 MAP kinase (MAPK) has an integral role in modulating inflammatory processes in autoimmunity. Conditionally knocking p38 MAPK out of myeloid cells in B6 mice shows a sexually dimorphic response to disease, which can be reversed by removal of sex hormones. This suggests that sex hormones may modulate the role of p38 MAPK. It is hypothesized that pathogenic inflammation in the animal model of MS, experimental autoimmune encephalomyelitis (EAE), is p38-independent in the presence of androgens and p38-dependent in the presence of estrogens. We tested this hypothesis by conditional or global genetic ablation of the primary mediator of androgenic effects, the androgen receptor (AR). Both in vivo and in vitro techniques were used to assess how AR signaling impacts the role of p38 in EAE pathogenesis and macrophage function. In vivo results from p38WT global AR knockout mice show no direct impact of AR signaling on EAE pathogenesis. In vitro results show no effect of androgens on pharmacologic p38 inhibition in the immortalized cell line RAW 264.7 macrophages. EAE results from p38 conditional knockout and AR knockout mice are pending.