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RESEARCH PRODUCT

Astrocytic Calcium Waves Signal Brain Injury to Neural Stem and Progenitor Cells

Ruth Von LaerHelmut KettenmannEduardo Rosales JubalEduardo Rosales JubalAdriana RochaMoyo GrebbinAlbrecht StrohMartin ZenkeAnna KraftClaudia DöringStefan Momma

subject

Male0301 basic medicineTime FactorsNotch signaling pathwaySubventricular zonechemistry.chemical_elementBiologyCalciumcalcium signalingBiochemistryArticleMice03 medical and health sciencesAdenosine TriphosphateNeural Stem CellsDownregulation and upregulationCell MovementGeneticsmedicineAnimalsCell Self RenewalProgenitor celllcsh:QH301-705.5Cells CulturedCalcium signalinglcsh:R5-920Gene Expression ProfilingastrocytesGap JunctionsCell DifferentiationCell BiologyAnatomyHypoxia (medical)strokeNeural stem cellDisease Models Animal030104 developmental biologymedicine.anatomical_structurelcsh:Biology (General)chemistryBrain InjuriesCalciummedicine.symptomFunction and Dysfunction of the Nervous Systemlcsh:Medicine (General)TranscriptomeNeurosciencenotchDevelopmental Biology

description

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 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.

10.1016/j.stemcr.2017.01.009http://dx.doi.org/10.1016/j.stemcr.2017.01.009