Review: A Novel Multiple Sclerosis Model Utilizing Cuprizone and Rapamycin

Abstract

Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system leading to debilitating long-term neurologic damage, primarily due to axonal loss following unsuccessful remyelination and the limited ability to remyelinate in the adult human brain. This review summarizes the current knowledge regarding 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 simultaneously with demyelination due to ongoing oligodendrocyte progenitor cell (OPC) 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 demyelinating diseases, such as MS.