Frankfurt University Medical School Frankfurt

Frankfurt am Main, Germany

Frankfurt University Medical School Frankfurt

Frankfurt am Main, Germany
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Kraft A.,Frankfurt University Medical School Frankfurt | Jubal E.R.,Johannes Gutenberg University Mainz | Jubal E.R.,Diego Portales University | von Laer R.,Frankfurt University Medical School Frankfurt | And 7 more authors.
Stem Cell Reports | Year: 2017

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 their self-renewal as well as migratory behavior. These changes are due to an upregulation of the Notch signaling pathway. This introduces the concept of propagating astrocytic calcium waves transmitting brain injury signals over long distances. Based on gene profiling data in a stroke model, Momma and colleagues hypothesize a role of calcium signaling in the stem cell injury response. Using a newly established in vitro model they show that astrocytic calcium waves spread to neural stem and progenitor cells, thereby increasing their self-renewal and migration capacity. These effects are mediated by the Notch/Hes1 signaling pathway. © 2017 The Author(s).


Ridder K.,Frankfurt University Medical School Frankfurt | Ridder K.,German Cancer Research Center | Keller S.,German Cancer Research Center | Dams M.,Frankfurt University Medical School Frankfurt | And 20 more authors.
PLoS Biology | Year: 2014

Mechanisms behind how the immune system signals to the brain in response to systemic inflammation are not fully understood. Transgenic mice expressing Cre recombinase specifically in the hematopoietic lineage in a Cre reporter background display recombination and marker gene expression in Purkinje neurons. Here we show that reportergene expression in neurons is caused by intercellular transfer of functional Cre recombinase messenger RNA from immune cells into neurons in the absence of cell fusion. In vitro purified secreted extracellular vesicles (EVs) from blood cells contain Cre mRNA, which induces recombination in neurons when injected into the brain. Although Cre-mediated recombination events in the brain occur very rarely in healthy animals, their number increases considerably in different injury models, particularly under inflammatory conditions, and extend beyond Purkinje neurons to other neuronal populations in cortex, hippocampus, and substantia nigra. Recombined Purkinje neurons differ in their miRNA profile from their nonrecombined counterparts, indicating physiological significance. These observations reveal the existence of a previously unrecognized mechanism to communicate RNA-based signals between the hematopoietic system and various organs, including the brain, in response to inflammation. © 2014 Ridder et al.

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