Date of Award
Multiple sclerosis -- Animal models, Myelination, Rapamycin
Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system leading to debilitating long-term neurologic damage, primarily due to the limited ability of remyelination in the adult human brain. This review summarizes the current knowledge regarding the combined administration of Cuprizone (CPZ) and rapamycin as a novel animal model for MS. Utilization of CPZ induces non-immune mediated demyelination, therefore bypassing complexities of the immune system and allowing analysis of de-/remyelination. Furthermore, remyelination occurs simultaneous with demyelination due to ongoing oligodendrocyte progenitor cells (OPCs) differentiation into mature oligodendrocytes (OLGs).
The immunosuppressive agent, rapamycin inhibits the regulatory pathway Akt/mTOR, which primarily controls myelination. This inhibition prevents ongoing OPCs from differentiating into mature oligodendrocytes (OLGs), therefore preventing myelination. The dual CPZ/rapamycin model produces more complete demyelination and a slowed remyelination phase. The long-term relevance of this review is to assess distinct stages and contributors of de-/remyelination in MS to better assess possible therapeutics for patients diagnosed with the disease.
Bahri, Mara, "Review: A Novel Multiple Sclerosis Model Utilizing Cuprizone and Rapamycin" (2016). University Honors Theses. Paper 341.