Cuprizone-Induced demyelination in CNP::GFP transgenic mice

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 nucle...

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Publicado: 2010
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Acceso en línea:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219967_v518_n12_p2261_Silvestroff
http://hdl.handle.net/20.500.12110/paper_00219967_v518_n12_p2261_Silvestroff
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spelling paper:paper_00219967_v518_n12_p2261_Silvestroff2023-06-08T14:45:00Z Cuprizone-Induced demyelination in CNP::GFP transgenic mice Cuprizone Demyelination Oligodendrocytes Remyelination 2',3' cyclic nucleotide 3' phosphodiesterase cuprizone green fluorescent protein myelin basic protein adult animal animal cell animal cell culture animal experiment animal model animal tissue anterior commissure antibody specificity article astrocytosis brain cortex brain stem caudate nucleus cell activation cell damage central nervous system controlled study corpus callosum demyelination hippocampus immunohistochemistry microglia microphotography microscopy mouse nonhuman olfactory bulb oligodendroglia optic chiasm priority journal protein expression putamen quantitative analysis tissue section transgenic mouse 2',3'-Cyclic-Nucleotide Phosphodiesterases Animals Astrocytes Brain Cell Count Cell Proliferation Cuprizone Demyelinating Diseases Glial Fibrillary Acidic Protein Gliosis Green Fluorescent Proteins Mice Mice, Inbred C57BL Mice, Transgenic Microglia Myelin Basic Proteins Neurons Oligodendroglia Promoter Regions, Genetic 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′-phosphodies-terase (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. © 2010 Wiley-Liss, Inc. 2010 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219967_v518_n12_p2261_Silvestroff http://hdl.handle.net/20.500.12110/paper_00219967_v518_n12_p2261_Silvestroff
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-134
collection Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic Cuprizone
Demyelination
Oligodendrocytes
Remyelination
2',3' cyclic nucleotide 3' phosphodiesterase
cuprizone
green fluorescent protein
myelin basic protein
adult animal
animal cell
animal cell culture
animal experiment
animal model
animal tissue
anterior commissure
antibody specificity
article
astrocytosis
brain cortex
brain stem
caudate nucleus
cell activation
cell damage
central nervous system
controlled study
corpus callosum
demyelination
hippocampus
immunohistochemistry
microglia
microphotography
microscopy
mouse
nonhuman
olfactory bulb
oligodendroglia
optic chiasm
priority journal
protein expression
putamen
quantitative analysis
tissue section
transgenic mouse
2',3'-Cyclic-Nucleotide Phosphodiesterases
Animals
Astrocytes
Brain
Cell Count
Cell Proliferation
Cuprizone
Demyelinating Diseases
Glial Fibrillary Acidic Protein
Gliosis
Green Fluorescent Proteins
Mice
Mice, Inbred C57BL
Mice, Transgenic
Microglia
Myelin Basic Proteins
Neurons
Oligodendroglia
Promoter Regions, Genetic
spellingShingle Cuprizone
Demyelination
Oligodendrocytes
Remyelination
2',3' cyclic nucleotide 3' phosphodiesterase
cuprizone
green fluorescent protein
myelin basic protein
adult animal
animal cell
animal cell culture
animal experiment
animal model
animal tissue
anterior commissure
antibody specificity
article
astrocytosis
brain cortex
brain stem
caudate nucleus
cell activation
cell damage
central nervous system
controlled study
corpus callosum
demyelination
hippocampus
immunohistochemistry
microglia
microphotography
microscopy
mouse
nonhuman
olfactory bulb
oligodendroglia
optic chiasm
priority journal
protein expression
putamen
quantitative analysis
tissue section
transgenic mouse
2',3'-Cyclic-Nucleotide Phosphodiesterases
Animals
Astrocytes
Brain
Cell Count
Cell Proliferation
Cuprizone
Demyelinating Diseases
Glial Fibrillary Acidic Protein
Gliosis
Green Fluorescent Proteins
Mice
Mice, Inbred C57BL
Mice, Transgenic
Microglia
Myelin Basic Proteins
Neurons
Oligodendroglia
Promoter Regions, Genetic
Cuprizone-Induced demyelination in CNP::GFP transgenic mice
topic_facet Cuprizone
Demyelination
Oligodendrocytes
Remyelination
2',3' cyclic nucleotide 3' phosphodiesterase
cuprizone
green fluorescent protein
myelin basic protein
adult animal
animal cell
animal cell culture
animal experiment
animal model
animal tissue
anterior commissure
antibody specificity
article
astrocytosis
brain cortex
brain stem
caudate nucleus
cell activation
cell damage
central nervous system
controlled study
corpus callosum
demyelination
hippocampus
immunohistochemistry
microglia
microphotography
microscopy
mouse
nonhuman
olfactory bulb
oligodendroglia
optic chiasm
priority journal
protein expression
putamen
quantitative analysis
tissue section
transgenic mouse
2',3'-Cyclic-Nucleotide Phosphodiesterases
Animals
Astrocytes
Brain
Cell Count
Cell Proliferation
Cuprizone
Demyelinating Diseases
Glial Fibrillary Acidic Protein
Gliosis
Green Fluorescent Proteins
Mice
Mice, Inbred C57BL
Mice, Transgenic
Microglia
Myelin Basic Proteins
Neurons
Oligodendroglia
Promoter Regions, Genetic
description 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′-phosphodies-terase (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. © 2010 Wiley-Liss, Inc.
title Cuprizone-Induced demyelination in CNP::GFP transgenic mice
title_short Cuprizone-Induced demyelination in CNP::GFP transgenic mice
title_full Cuprizone-Induced demyelination in CNP::GFP transgenic mice
title_fullStr Cuprizone-Induced demyelination in CNP::GFP transgenic mice
title_full_unstemmed Cuprizone-Induced demyelination in CNP::GFP transgenic mice
title_sort cuprizone-induced demyelination in cnp::gfp transgenic mice
publishDate 2010
url https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219967_v518_n12_p2261_Silvestroff
http://hdl.handle.net/20.500.12110/paper_00219967_v518_n12_p2261_Silvestroff
_version_ 1768545128514846720