Date of Award
Spring 2021
Rights
Access is available to all users
Document Type
Thesis
Degree Name
Master of Science (MS) in Biology
Department
Biology
Abstract
Gamma aminobutyric acid (GABA) is an inhibitory neurotransmitter, produced by neurons in the central nervous system (CNS) and by some species of intestinal bacteria. GABAA receptors are found not only in the CNS, but also in T cells and within the intestines. Past studies have indicated that GABA can have an anti-inflammatory effect and production of GABA by gut bacteria decreases in patients with multiple sclerosis (MS). We examined whether administration of a positive allosteric GABAA receptor modulator, farnesol, ameliorates the progression of experimental autoimmune encephalomyelitis (EAE), a murine model of MS and whether those effects correlated with a decrease in immune cell infiltration of the central nervous system. We observed a significant treatment effect on clinical scores, as well as immune cell infiltration. Seeking to determine if these effects were due to GABAA receptor activation or other anti-inflammatory effects of farnesol, we investigated whether modifying mice microbiota with GABA-producing bacteria influences EAE severity. We used a Lactococcus lactis strain (P8 GAD-L. lactis) genetically modified with an extra copy of glutamic acid decarboxylase (GAD) and glutamic acid/glutamate antiporter to produce high levels of GABA (Castillo, unpublished data). P8 GAD-L.lactis produced significantly more GABA than the L. lactis control strain (pAC-L. lactis). EAE-induced C57BL/6 mice treated with P8 GAD-L. lactis (n=10) had significantly lower clinical scores than the sham control group (autoclaved media; n=10) and the L. lactis control group (pAC-L.lactis; n=10). Despite trying, we were unable to repeat this experiment due to difficulties inducing disease. We farther tested different C57BL/6 mouse providers (Envigo and Jackson Laboratory) to determine if the decrease in disease severity resulted from the provider (Envigo). The Envigo group (n=10) had fewer animals die from severe EAE compared to the Jackson group (n=10), but it wasn’t significant. More experiments are needed to determine what may be causing this difference in disease severity and if oral treatment with a GABA producing probiotic protects against mouse EAE.
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Recommended Citation
Kohl, Hannah M., "Investigating the protective effects of intestinal GABA[subscript A] receptor activation on an animal model of Multiple Sclerosis" (2021). EWU Masters Thesis Collection. 692.
https://dc.ewu.edu/theses/692
