Primary Faculty Mentor Name

Gary Mawe

Project Collaborators

Friederike Uhlig, Melody M Haag, Brigitte Lavoie, Gary M Mawe

Status

Undergraduate

Student College

College of Arts and Sciences

Program/Major

Neuroscience

Primary Research Category

Biological Sciences

Presentation Title

Using the EAE mouse model to understand constipation in MS

Time

9:00 AM

Location

Silver Maple Ballroom - Biological Sciences

Abstract

Multiple Sclerosis (MS) is an autoimmune disease that causes a myriad of symptoms, including cognitive, sensory, and motor deficits, as well as gastrointestinal (GI) dysmotility. We have previously demonstrated that male mice with experimental autoimmune encephalomyelitis (EAE), the predominant model for MS, have disrupted motility, but the mechanisms for this dysmotility are not understood, and potential sex differences have not been evaluated. Since 5-hydroxytrptamine (5-HT; serotonin) is a mediator of motor and secretory reflexes in the gut, I investigated key elements of mucosal 5-HT signaling in the EAE mouse model of MS. Enzyme linked immunosorbent assay (ELISA) was used to evaluate 5-HT levels as normalized by a bicinchoninic acid assay and RT-qPCR was used to evaluate mRNA levels for the rate limiting molecule in 5-HT synthesis, tryptophan hydroxylase 1 (Tph1), and the serotonin reuptake transporter (SERT), both of which were normalized to the housekeeping gene beta 2 macroglobulin (B2M). I also compared motility and fecal composition in male versus female mice with EAE. The mRNA level for Tph1 was decreased in EAE mice, but levels of 5-HT in the tissue and SERT mRNA levels were unchanged. Furthermore, no differences were detected in colonic motility, fecal water content, or whole gut transit in male versus female mice with EAE. However, it was noted that male mice with EAE displayed peak GI dysfunction at day 21, whereas female mice with EAE showed peak dysfunction at day 27. These findings indicate that male and female mice represent comparable models for motility disruption in EAE, and suggest that mechanisms other than altered 5-HT signaling are responsible for altered motility in this model.

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Using the EAE mouse model to understand constipation in MS

Multiple Sclerosis (MS) is an autoimmune disease that causes a myriad of symptoms, including cognitive, sensory, and motor deficits, as well as gastrointestinal (GI) dysmotility. We have previously demonstrated that male mice with experimental autoimmune encephalomyelitis (EAE), the predominant model for MS, have disrupted motility, but the mechanisms for this dysmotility are not understood, and potential sex differences have not been evaluated. Since 5-hydroxytrptamine (5-HT; serotonin) is a mediator of motor and secretory reflexes in the gut, I investigated key elements of mucosal 5-HT signaling in the EAE mouse model of MS. Enzyme linked immunosorbent assay (ELISA) was used to evaluate 5-HT levels as normalized by a bicinchoninic acid assay and RT-qPCR was used to evaluate mRNA levels for the rate limiting molecule in 5-HT synthesis, tryptophan hydroxylase 1 (Tph1), and the serotonin reuptake transporter (SERT), both of which were normalized to the housekeeping gene beta 2 macroglobulin (B2M). I also compared motility and fecal composition in male versus female mice with EAE. The mRNA level for Tph1 was decreased in EAE mice, but levels of 5-HT in the tissue and SERT mRNA levels were unchanged. Furthermore, no differences were detected in colonic motility, fecal water content, or whole gut transit in male versus female mice with EAE. However, it was noted that male mice with EAE displayed peak GI dysfunction at day 21, whereas female mice with EAE showed peak dysfunction at day 27. These findings indicate that male and female mice represent comparable models for motility disruption in EAE, and suggest that mechanisms other than altered 5-HT signaling are responsible for altered motility in this model.