Oligodendrocytes in mouse corpus callosum are coupled via gap junction channels formed by connexin47 and connexin32.
According to previously published ultrastructural studies, oligodendrocytes in white matter exhibit gap junctions with astrocytes, but not among each other, while in vitro oligodendrocytes form functional gap junctions. We have studied functional coupling among oligodendrocytes in acute slices of postnatal mouse corpus callosum. By whole-cell patch clamp we dialyzed oligodendrocytes with biocytin, a gap junction-permeable tracer. On average 61 cells were positive for biocytin detected by labeling with streptavidin-Cy3. About 77% of the coupled cells stained positively for the oligodendrocyte marker protein CNPase, 9% for the astrocyte marker GFAP and 14% were negative for both CNPase and GF…
Building Bridges through Science
WOS: 000415310800007 PubMed ID: 29144972 Science is ideally suited to connect people from different cultures and thereby foster mutual understanding. To promote international life science collaboration, we have launched "The Science Bridge'' initiative. Our current project focuses on partnership between Western and Middle Eastern neuroscience communities. Medical Research Council [MC_UP_1202/5]
Membrane-type 1 metalloproteinase is upregulated in microglia/brain macrophages in neurodegenerative and neuroinflammatory diseases
We previously reported that glioma cells induce the expression of membrane-type 1 metalloproteinase (MT1-MMP or MMP-14) in tumor-associated microglia/macrophages and promote tumor growth, whereas MMP-14 expression in microglia under physiological conditions is very low. Here, we show that the increase in MMP-14 expression is also found in microglia/macrophages associated with neurodegenerative and neuroinflammatory pathologies in mouse models as well as in human biopsies or post-mortem tissue. We found that microglial/macrophage MMP-14 expression was upregulated in Alzheimer's disease tissue, in active lesions of multiple sclerosis, and in tissue from stage II stroke as well as in the corre…
Tyrphostin AG126 exerts neuroprotection in CNS inflammation by a dual mechanism
The putative protein tyrosine kinase (PTK) inhibitor tyrphostin AG126 has proven beneficial in various models of inflammatory disease. Yet molecular targets and cellular mechanisms remained enigmatic. We demonstrate here that AG126 treatment has beneficial effects in experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. AG126 alleviates the clinical symptoms, diminishes encephalitogenic Th17 differentiation, reduces inflammatory CNS infiltration as well as microglia activation and attenuates myelin damage. We show that AG126 directly inhibits Bruton's tyrosine kinase (BTK), a PTK associated with B cell receptor and Toll-like receptor (TLR) signaling. However, BTK …
Astrocytic Calcium Waves Signal Brain Injury to Neural Stem and Progenitor Cells
Summary Brain injuries, such as stroke or trauma, induce neural stem cells in the subventricular zone (SVZ) to a neurogenic response. Very little is known about the molecular cues that signal tissue damage, even over large distances, to the SVZ. Based on our analysis of gene expression patterns in the SVZ, 48 hr after an ischemic lesion caused by middle cerebral artery occlusion, we hypothesized that the presence of an injury might be transmitted by an astrocytic traveling calcium wave rather than by diffusible factors or hypoxia. Using a newly established in vitro system we show that calcium waves induced in an astrocytic monolayer spread to neural stem and progenitor cells and increase th…