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Date of Award

Spring 2020

Rights

Access perpetually restricted to EWU users with an active EWU NetID

Document Type

Thesis: EWU Only

Degree Name

Master of Science (MS) in Biology

Department

Biology

Abstract

Farnesol (FOL) is a naturally-produced 15-carbon organic acyclic sesquiterpene alcohol (isoprenol) that acts as a potent blocker of neuronal voltage-gated Ca2+ channels (L- and N-type) and is found in the human brain. FOL has potent anti-oxidant and antiinflammatory effects in vitro and is neuroprotective in a murine model of neurotoxicity. Because inflammation and neurodegeneration are mechanisms associated with CNS demyelinating diseases, we sought to determine whether FOL treatment would result in protection against experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. We demonstrate that there is a correlation between reduced neuroinflammation and EAE severity observed in the context of FOL protection. We compared the progression of EAE in MOG35-55 immunized female C57BL/6 mice treated orally with FOL (100 mg/kg/daily) emulsified in corn oil, versus vehicle-treated and untreated EAE mice. FOL significantly reduced the average clinical scores of EAE mice when compared to untreated mice and vehicle-treated mice. The protective effect was associated with a significant reduction of CD4+ T cell spinal cord infiltration in FOL-treated mice as assessed by flow cytometry. Although FOL’s mechanism of action remains to be known, we propose that FOL promotes protection against CNS inflammatory demyelination by promoting an anti-inflammatory effect in the periphery. We compared pro-inflammatory cytokine transcriptional levels in brain tissues of EAE mice. The potential benefit of FOL nanoencapsulation in neuroprotection was explored. Understanding the neuroprotective effects of FOL may provide insight to novel therapeutic approaches for MS.

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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