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Cuprizone-induced demyelination and demyelination-associated inflammation result in different proton magnetic resonance metabolite spectra.

Praet J, Orije J, Kara F, Guglielmetti C, Santermans E, Daans J, Hens N, Verhoye M, Berneman Z, Ponsaerts P, Van der Linden A - NMR Biomed (2015)

Bottom Line: In this study we aimed to better understand the changes in metabolite concentrations following demyelination of the white matter.Therefore, (1) H-MRS might possibly allow us to discriminate demyelination from demyelination-associated inflammation via changes in Tau and Glu concentration.In addition, the observed decrease in tCho concentration in cuprizone-induced demyelinating lesions should be further explored as a possible diagnostic tool for the early identification of human MS type III lesions.

View Article: PubMed Central - PubMed

Affiliation: Experimental Cell Transplantation Group, Laboratory of Experimental Hematology, University of Antwerp, Antwerp, Belgium; Vaccine and Infectious Disease Institute (Vaxinfectio), University of Antwerp, Antwerp, Belgium; Bio-Imaging Laboratory, University of Antwerp, Antwerp, Belgium.

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Representative immunofluorescence images taken from the splenium of control and CPZ-treated CX3CR1+/+, CX3CR1+/− and CX3CR1−/− mice. All images were taken from the same reference point and the splenium is delineated using thin white lines. TOPRO-3 staining (first column) visualizes total cell density (in purple, false color image). IBA1 staining or direct eGFP fluorescence (second column) visualizes microglial density (in green). CC1 staining (second column) visualizes oligodendrocyte density (in red). MBP staining (third column) visualizes myelination (in red). S100β staining (fourth column) visualizes oligodendrocyte density (in red). GFAP staining (fourth column) visualizes astrogliosis (in blue). Scale bars indicate 100 µm.
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fig01: Representative immunofluorescence images taken from the splenium of control and CPZ-treated CX3CR1+/+, CX3CR1+/− and CX3CR1−/− mice. All images were taken from the same reference point and the splenium is delineated using thin white lines. TOPRO-3 staining (first column) visualizes total cell density (in purple, false color image). IBA1 staining or direct eGFP fluorescence (second column) visualizes microglial density (in green). CC1 staining (second column) visualizes oligodendrocyte density (in red). MBP staining (third column) visualizes myelination (in red). S100β staining (fourth column) visualizes oligodendrocyte density (in red). GFAP staining (fourth column) visualizes astrogliosis (in blue). Scale bars indicate 100 µm.

Mentions: In order to investigate the role of CX3CL1/CX3CR1 signaling during the inflammatory phase of CPZ-induced CNS demyelination, six experimental mouse groups were included in two independent experiments, and shown here are the pooled data from (a) wild type CX3CR1+/+ C57BL/6 mice at the age of 12 weeks (n = 7), (b) wild type CX3CR1+/+ C57BL/6 mice at the age of 12 weeks that received a 0.2% CPZ-supplemented diet between the age of 8 and 12 weeks (n = 7), (c) transgenic CX3CR1+/− C57BL/6 mice, in which one copy of the CX3CR1 gene is replaced by the eGFP reporter gene, at the age of 12 weeks (n = 7), (d) transgenic CX3CR1+/− C57BL/6 mice at the age of 12 weeks that received a 0.2% CPZ-supplemented diet between the age of 8 and 12 weeks (n = 8), (e) transgenic CX3CR1−/− C57BL/6 mice, in which both copies of the CX3CR1 gene are replaced by the eGFP reporter gene, at the age of 12 weeks (n = 7) and (f) transgenic CX3CR1+/− C57BL/6 mice at the age of 12 weeks that received a 0.2% CPZ-supplemented diet between the age of 8 and 12 weeks (n = 7). Note that mice receiving the 0.2% CPZ-supplemented diet do not lose weight, but fail to gain weight when compared with mice on standard rodent chow. Fig.1 provides an overview of representative immunofluorescence images taken from the splenium at the age of 12 weeks for each of the different groups. For clarity, the exact anatomical localization of the images is provided in Supplementary File S2 and larger images of those provided in Fig.1 are provided in Supplementary File S3. On each of the images, the splenium is delineated by a white dotted line. Note that thickness of the splenium varies between experimental groups, as the presence of an inflammatory reaction causes swelling of the splenium. Within the splenium, total cell density (no of nuclei/mm2), oligodendrocyte density (no of CC1+ cells/mm2), microglial density (no of IBA1+ or eGFP+ cells/mm2), astrocyte density (no of S100β + cells/mm2), degree of astrogliosis (% O.D. GFAP) and degree of myelination (% O.D. MBP) were quantified and plotted in Fig.2 for each of the groups.


Cuprizone-induced demyelination and demyelination-associated inflammation result in different proton magnetic resonance metabolite spectra.

Praet J, Orije J, Kara F, Guglielmetti C, Santermans E, Daans J, Hens N, Verhoye M, Berneman Z, Ponsaerts P, Van der Linden A - NMR Biomed (2015)

Representative immunofluorescence images taken from the splenium of control and CPZ-treated CX3CR1+/+, CX3CR1+/− and CX3CR1−/− mice. All images were taken from the same reference point and the splenium is delineated using thin white lines. TOPRO-3 staining (first column) visualizes total cell density (in purple, false color image). IBA1 staining or direct eGFP fluorescence (second column) visualizes microglial density (in green). CC1 staining (second column) visualizes oligodendrocyte density (in red). MBP staining (third column) visualizes myelination (in red). S100β staining (fourth column) visualizes oligodendrocyte density (in red). GFAP staining (fourth column) visualizes astrogliosis (in blue). Scale bars indicate 100 µm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4403969&req=5

fig01: Representative immunofluorescence images taken from the splenium of control and CPZ-treated CX3CR1+/+, CX3CR1+/− and CX3CR1−/− mice. All images were taken from the same reference point and the splenium is delineated using thin white lines. TOPRO-3 staining (first column) visualizes total cell density (in purple, false color image). IBA1 staining or direct eGFP fluorescence (second column) visualizes microglial density (in green). CC1 staining (second column) visualizes oligodendrocyte density (in red). MBP staining (third column) visualizes myelination (in red). S100β staining (fourth column) visualizes oligodendrocyte density (in red). GFAP staining (fourth column) visualizes astrogliosis (in blue). Scale bars indicate 100 µm.
Mentions: In order to investigate the role of CX3CL1/CX3CR1 signaling during the inflammatory phase of CPZ-induced CNS demyelination, six experimental mouse groups were included in two independent experiments, and shown here are the pooled data from (a) wild type CX3CR1+/+ C57BL/6 mice at the age of 12 weeks (n = 7), (b) wild type CX3CR1+/+ C57BL/6 mice at the age of 12 weeks that received a 0.2% CPZ-supplemented diet between the age of 8 and 12 weeks (n = 7), (c) transgenic CX3CR1+/− C57BL/6 mice, in which one copy of the CX3CR1 gene is replaced by the eGFP reporter gene, at the age of 12 weeks (n = 7), (d) transgenic CX3CR1+/− C57BL/6 mice at the age of 12 weeks that received a 0.2% CPZ-supplemented diet between the age of 8 and 12 weeks (n = 8), (e) transgenic CX3CR1−/− C57BL/6 mice, in which both copies of the CX3CR1 gene are replaced by the eGFP reporter gene, at the age of 12 weeks (n = 7) and (f) transgenic CX3CR1+/− C57BL/6 mice at the age of 12 weeks that received a 0.2% CPZ-supplemented diet between the age of 8 and 12 weeks (n = 7). Note that mice receiving the 0.2% CPZ-supplemented diet do not lose weight, but fail to gain weight when compared with mice on standard rodent chow. Fig.1 provides an overview of representative immunofluorescence images taken from the splenium at the age of 12 weeks for each of the different groups. For clarity, the exact anatomical localization of the images is provided in Supplementary File S2 and larger images of those provided in Fig.1 are provided in Supplementary File S3. On each of the images, the splenium is delineated by a white dotted line. Note that thickness of the splenium varies between experimental groups, as the presence of an inflammatory reaction causes swelling of the splenium. Within the splenium, total cell density (no of nuclei/mm2), oligodendrocyte density (no of CC1+ cells/mm2), microglial density (no of IBA1+ or eGFP+ cells/mm2), astrocyte density (no of S100β + cells/mm2), degree of astrogliosis (% O.D. GFAP) and degree of myelination (% O.D. MBP) were quantified and plotted in Fig.2 for each of the groups.

Bottom Line: In this study we aimed to better understand the changes in metabolite concentrations following demyelination of the white matter.Therefore, (1) H-MRS might possibly allow us to discriminate demyelination from demyelination-associated inflammation via changes in Tau and Glu concentration.In addition, the observed decrease in tCho concentration in cuprizone-induced demyelinating lesions should be further explored as a possible diagnostic tool for the early identification of human MS type III lesions.

View Article: PubMed Central - PubMed

Affiliation: Experimental Cell Transplantation Group, Laboratory of Experimental Hematology, University of Antwerp, Antwerp, Belgium; Vaccine and Infectious Disease Institute (Vaxinfectio), University of Antwerp, Antwerp, Belgium; Bio-Imaging Laboratory, University of Antwerp, Antwerp, Belgium.

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Related in: MedlinePlus