Defense Date
2024
Document Type
Thesis
Degree Name
Master of Science
Department
Anatomy & Neurobiology
First Advisor
CARMEN SATO-BIGBEE
Abstract
Our laboratory showed that elevated levels of the endogenous peptide Nociceptin inhibit oligodendrocyte maturation, preventing untimely precocious brain myelination. We now have found that Nociceptin expression is also significantly increased in the most severe “progressive” forms of multiple sclerosis (PMS). This posed the question of whether Nociceptin plays a role in the arrested oligodendrocyte maturation observed in PMS, thus obstructing remyelination. To test this possibility, this study developed a model of PMS by inducing experimental autoimmune encephalomyelitis (EAE) in older mice. Our findings showed that, like in humans with PMS, older EAE animals develop persistent and highly debilitating clinical symptoms. These older animals also show an increase in brain activated microglia and reactive astrocytes, accompanied by an increasing trend in Nociceptin levels. Together with the observed severe brain demyelination, these characteristics are indicative of an animal model that provides an important tool to investigate Nociceptin role in the pathogenesis of PMS.
Rights
© JOSEPH BAKER
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
8-8-2024