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Massimiliano Cristofanilli, PhD (Tisch MS) presented the following article in Journal Club.
Article title: CXCR4 Signaling Regulates Remyelination by Endogenous Oligodendrocyte Progenitor Cells in a Viral Model of Demyelination
Reference: Carbajal KS, Miranda JL, Tsukamoto MR and Lane TE. GLIA 2011 December; Volume 59, Issue 12,pages 1813–1821.
Multiple sclerosis is characterized by inflammatory lesions causing damage to the myelin sheath, a layer of insulation protecting and enhancing the conductive capabilities of the axons of the central nervous system. In early stages of the disease, demyelinated areas are partially repaired by oligodendrocyte progenitor cells (OPCs), the precursors of the cells responsible for the production of myelin. Over time, however, the remyelinating effect diminishes as OPCs become less responsive to MS lesions and fewer OPCs are present at damaged sites and fewer of those that are present mature into oligodendrocytes capable of myelin production.
In the present study, myelin loss to MS was simulated by infecting mice with a strain of mouse hepatitis virus that induced widespread myelin destruction, and it was found that the receptor protein CXCR4 -- ordinarily sensitive to the chemical signals released in response to myelin damage -- plays a key role in regulating the proliferation and maturation of OPCs. Mice treated with an inhibitor of CXCR4 were found to have a significantly increased number of OPCs and fewer mature oligodendrocytes. When treatment with the CXCR4 inhibitor ended and the mice were allowed to recover, their reservoir of mature oligodendrocytes was expanded and both remyelination and clinical outcomes improved. These findings suggest therapeutic strategies directed at the manipulation of the supply of OPCs and their maturation into oligodendrocytes.