Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 4 de 4
Filter
Add more filters










Database
Language
Publication year range
1.
Neuroimage ; 59(3): 2678-88, 2012 Feb 01.
Article in English | MEDLINE | ID: mdl-21914485

ABSTRACT

Magnetic resonance imaging (MRI) is the gold standard for the detection of multiple sclerosis (MS) lesions. However, current MRI techniques provide little information about the structural features of a brain lesion with inflammatory cell infiltration, demyelination, gliosis, acute axonal damage and axonal loss. To identify methods for a differentiation of demyelination, inflammation, and axonal damage we developed a novel mouse model combining cuprizone-induced demyelination and experimental autoimmune encephalomyelitis. MS-like brain lesions were assessed by T1-weighted, T2-weighted, and magnetization transfer MRI as well as by diffusion tensor imaging (DTI). T2-weighted MRI differentiated control and diseased mice, while T1-weighted MRI better reflected the extent of inflammation and axonal damage. In DTI, axonal damage and cellular infiltration led to a reduction of the axial diffusivity, whereas primary demyelination after cuprizone treatment was reflected by changes in radial but not axial diffusivity. Importantly, alterations in radial diffusivity were less pronounced in mice with demyelination, inflammation, and acute axonal damage, indicating that radial diffusivity may underestimate demyelination in acute MS lesions. In conclusion, the combined information from different DTI parameters allows for a more precise identification of solely demyelinated lesions versus demyelinated and acutely inflamed lesions. These findings are of relevance for offering individualized, stage-adapted therapies for MS patients.


Subject(s)
Brain/pathology , Diffusion Tensor Imaging/methods , Encephalomyelitis, Autoimmune, Experimental/pathology , Magnetic Resonance Imaging/methods , Multiple Sclerosis/pathology , Animals , Axons/pathology , Blood-Brain Barrier/pathology , Cuprizone , Demyelinating Diseases/pathology , Discriminant Analysis , Encephalomyelitis, Autoimmune, Experimental/chemically induced , Female , Gliosis/pathology , Image Processing, Computer-Assisted/methods , Inflammation/pathology , Mice , Mice, Inbred C57BL , Monoamine Oxidase Inhibitors , Multiple Sclerosis/chemically induced , Pertussis Toxin/toxicity
2.
Eur J Immunol ; 41(3): 833-44, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21287545

ABSTRACT

PI3Ks control signal transduction triggered by growth factors and G-protein-coupled receptors and regulate an array of biological processes, including cellular proliferation, differentiation, survival and migration. Herein, we investigated the role of PI3Kγ in the pathogenesis of EAE. We show that, in the absence of PI3Kγ expression, clinical signs of EAE were delayed and mitigated. PI3Kγ-deficient myelin oligodendrocyte glycoprotein (MOG)(35-55) -specific CD4(+) T cells appeared later in the secondary lymphoid organs and in the CNS than their WT counterparts. Transfer of WT CD4(+) cells into PI3Kγ(-/-) mice prior to MOG(35-55) immunisation restored EAE severity to WT levels, supporting the relevance of PI3Kγ expression in Th cells for the pathogenesis of EAE; however, PI3Kγ was dispensable for Th1 and Th17 differentiation, thus excluding an altered expression of these pathogenetically relevant cytokines as the cause for ameliorated EAE in PI3Kγ(-/-) mice. These findings demonstrate that PI3Kγ contributes to the development of autoimmune CNS inflammation.


Subject(s)
Class Ib Phosphatidylinositol 3-Kinase/deficiency , Encephalomyelitis, Autoimmune, Experimental/enzymology , Encephalomyelitis, Autoimmune, Experimental/prevention & control , Adoptive Transfer , Animals , Cell Differentiation , Class Ib Phosphatidylinositol 3-Kinase/genetics , Class Ib Phosphatidylinositol 3-Kinase/immunology , Encephalomyelitis, Autoimmune, Experimental/immunology , Encephalomyelitis, Autoimmune, Experimental/pathology , Glycoproteins/immunology , Lymphoid Tissue/immunology , Mice , Mice, Inbred C57BL , Mice, Knockout , Myelin-Oligodendrocyte Glycoprotein , Peptide Fragments/immunology , Phosphoinositide-3 Kinase Inhibitors , T-Lymphocytes, Helper-Inducer/enzymology , T-Lymphocytes, Helper-Inducer/immunology , T-Lymphocytes, Helper-Inducer/pathology , Time Factors
3.
Brain ; 129(Pt 11): 2992-3005, 2006 Nov.
Article in English | MEDLINE | ID: mdl-16844716

ABSTRACT

The amyloid beta-protein (Abeta) is the main component of Alzheimer's disease-related senile plaques. Although Abeta is associated with the development of Alzheimer's disease, it has not been shown which forms of Abeta induce neurodegeneration in vivo and which types of neurons are vulnerable. To address these questions, we implanted DiI crystals into the left frontocentral cortex of APP23 transgenic mice overexpressing mutant human APP (amyloid precursor protein gene) and of littermate controls. Traced commissural neurons in layer III of the right frontocentral cortex were quantified in 3-, 5-, 11- and 15-month-old mice. Three different types of commissural neurons were traced. At 3 months of age no differences in the number of labelled commissural neurons were seen in APP23 mice compared with wild-type mice. A selective reduction of the heavily ramified type of neurons was observed in APP23 mice compared with wild-type animals at 5, 11 and 15 months of age, starting when the first Abeta-deposits occurred in the frontocentral cortex at 5 months. The other two types of commissural neurons did not show alterations at 5 and 11 months. At 15 months, the number of traced sparsely ramified pyramidal neurons was reduced in addition to that of the heavily ramified neurons in APP23 mice compared with wild-type mice. At this time Abeta-deposits were seen in the neo- and allocortex as well as in the basal ganglia and the thalamus. In summary, our results show that Abeta induces progressive degeneration of distinct types of commissural neurons. Degeneration of the most vulnerable neurons starts in parallel with the occurrence of the first fibrillar Abeta-deposits in the neocortex, that is, with the detection of aggregated Abeta. The involvement of additional neuronal subpopulations is associated with the expansion of Abeta-deposition into further brain regions. The vulnerability of different types of neurons to Abeta, thereby, is presumably related to the complexity of their dendritic morphology.


Subject(s)
Alzheimer Disease/pathology , Amyloid beta-Peptides/physiology , Dendritic Cells/pathology , Neurons/pathology , Alzheimer Disease/metabolism , Amyloid beta-Peptides/metabolism , Animals , Axons/pathology , Blotting, Western , Disease Models, Animal , Disease Progression , Female , Mice , Mice, Transgenic , Neocortex/pathology , Plaque, Amyloid/pathology , Prosencephalon/metabolism
4.
J Bacteriol ; 185(2): 466-74, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12511492

ABSTRACT

The heat shock genes of Bacillus subtilis are assigned to four classes on the basis of their regulation mechanisms. While classes I and III are negatively controlled by two different transcriptional repressors, class II is regulated by the alternative sigma factor sigma(B). All heat shock genes with unidentified regulatory mechanisms, among them htpG, constitute class IV. Here, we show that expression of htpG is under positive control. We identified a DNA sequence (GAAAAGG) located downstream of the sigma(A)-dependent promoter of htpG. The heat inducibility of the promoter could be destroyed by inversion, nucleotide replacements, or removal of this DNA sequence. Fusion of this sequence to the vegetative lepA promoter conferred heat inducibility. Furthermore, we were able to show that the heat induction factor is dependent on the absolute temperature rather than the temperature increment and that nonnative proteins within the cytoplasm fail to induce htpG.


Subject(s)
Bacillus subtilis/growth & development , Gene Expression Regulation, Bacterial , HSP90 Heat-Shock Proteins/genetics , HSP90 Heat-Shock Proteins/metabolism , Hot Temperature , Regulatory Sequences, Nucleic Acid , Bacillus subtilis/genetics , Bacillus subtilis/physiology , Bacterial Proteins/chemistry , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Base Sequence , HSP90 Heat-Shock Proteins/chemistry , Heat-Shock Response , Molecular Sequence Data , Sigma Factor/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...