Cuprizone-induced demyelination in CNP::GFP transgenic mice.

Abstract

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 oligodendroglial (OLG) lineage, 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. Loss of GFP+ cells was accompanied by extensive astrogliosis and microglial activation, although neurons were not affected. Interestingly, cuprizone-treated animals showed both activation of GFAP expression and a higher proliferation rate in subventricular zone cells. A week after cuprizone removal from the diet, GFP+ oligodendroglial cells began repopulating the damaged structures. GFP expression precedes that of MBP and allows OLG detection before myelin restoration.

• Authors: Lucas Silvestroff, Sandra Bartucci, Eduardo Soto, Vittorio Gallo, Juana Pasquini, Paula Franco
• Journal: The Journal of comparative neurology (J Comp Neurol) Vol. 518 Issue 12 Pg. 2261-83 (Jun 15 2010) ISSN: 1096-9861 [Electronic] United States
• PMID: 20437527 (Publication Type: Journal Article)
• Copyright: Copyright 2010 Wiley-Liss, Inc.

Chemical References

• Glial Fibrillary Acidic Protein
• Myelin Basic Protein
• Green Fluorescent Proteins
• Cuprizone
• 2',3'-Cyclic-Nucleotide Phosphodiesterases

Topics

• 2',3'-Cyclic-Nucleotide Phosphodiesterases (genetics)
• Animals
• Astrocytes (metabolism, pathology)
• Brain (metabolism, pathology)
• Cell Count
• Cell Proliferation
• Cuprizone
• Demyelinating Diseases (chemically induced, metabolism, pathology)
• Glial Fibrillary Acidic Protein (metabolism)
• Gliosis (metabolism, pathology)
• Green Fluorescent Proteins (genetics, metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Microglia (metabolism, pathology)
• Myelin Basic Protein (metabolism)
• Neurons (metabolism, pathology)
• Oligodendroglia (metabolism, pathology)
• Promoter Regions, Genetic