Cuprizone- induced demyelination in CNP::GFP transgenic mice

BARTUCCI, S., SILVESTROFF, L., SOTO, E., GALLO V., PASQUINI, J. AND FRANCO P.

Mar del Plata- Argentina

Congreso; LIV Reunión Científica Anual de la Sociedad Argentina de investigación clínica y LVII Reunión Científica Anual de la Sociedad Argentina de Inmunología; 2009

SAIC

Cuprizone (bis-cyclohexanone oxaldihydrazone) was previously shown to induce demyelination in white matter enriched brain structures. In the present study we used the cuprizone demyelination model in transgenic mice expressing the enhanced green fluorescent protein (GFP) under the 2´-3´-cyclic nucleotide 3´-phosphodiesterase (CNPase) promoter. The use of these particular transgenic mice allows easy detection of cells belonging to the entire oligodendrocyte (OLG) linage, ranging from OLG precursors to mature myelinating OLGs. We were able to evaluate the precise extent of oligodendroglial cell damage and recovery within the murine adult central nervous system (CNS) after inducing demyelination by acute cuprizone intoxication. A generalized loss of GFP+ cells was observed after cuprizone exposure, and correlated with a decline in myelin basic protein (MBP) expression. OLGs were depleted in many brain areas that were previously thought to be unaffected by cuprizone treatment. Thus, in addition to the well known cuprizone effects on the medial corpus callosum, we also found a loss of GFP+ cells in most brain structures, particularly in the caudatus putamen, cortex, anterior commissure, olfactory bulb, hippocampus, optic chiasm, brainstem and cingulum. A week after cuprizone removal from the diet, GFP+ oligodendroglial cells began to repopulate the damaged structures. However, this recovery time was insufficient to allow a significant increase in MBP expression. Hence, during early remyelination stages, GFP expression precedes that of MBP and allows OLG detection before myelin restoration.