Date of Completion
College of Arts and Science Honors
Experimental Autoimmune Encephalomyelitis, Multiple Sclerosis, Mucosal 5-HT Signaling, Sex Differences, Enteric Nervous System, Gastrointestinal Dysfunction
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 GI motility, but the mechanisms for this dysmotility are not understood, and potential sex differences have not been evaluated. Since 5-hydroxytryptamine (5-HT; serotonin) is a mediator of motor and secretory reflexes in the gut, we 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 tissue levels as normalized by a bicinchoninic acid assay and RT-qPCR was used to evaluate mRNA expression 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 microglobulin (B2M). Motility and fecal composition were also compared in female versus male mice with EAE. The mRNA expression for Tph1 was decreased in EAE mice, but levels of 5-HT in the tissue and SERT mRNA expression were unchanged. Furthermore, no differences were detected in colonic motility, fecal water content, or whole GI transit in female versus male 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 GI dysfunction at day 27. These findings indicate that female and male mice present with similar levels of GI dysfunction over time, representing 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.
Holt, Emily Anne, "Evaluation of Mucosal 5-HT Signaling and Potential Sex Differences in Motor Activity in the Experimental Autoimmune Encephalomyelitis Mouse Model of Multiple Sclerosis" (2019). UVM College of Arts and Sciences College Honors Theses. 64.
Available for download on Sunday, May 02, 2021