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Author (up) Pfaender, S.; Fohr, K.; Lutz, A.-K.; Putz, S.; Achberger, K.; Linta, L.; Liebau, S.; Boeckers, T.M.; Grabrucker, A.M.
Title Cellular Zinc Homeostasis Contributes to Neuronal Differentiation in Human Induced Pluripotent Stem Cells Type Journal Article
Year 2016 Publication Neural Plasticity Abbreviated Journal Neural Plast
Volume 2016 Issue Pages 3760702
Keywords Apoptosis/physiology; Cell Survival/physiology; Homeostasis/*physiology; Humans; Induced Pluripotent Stem Cells/cytology/*metabolism; Neurogenesis/*physiology; Neurons/cytology/*metabolism; Signal Transduction/physiology; Zinc/*metabolism
Abstract Disturbances in neuronal differentiation and function are an underlying factor of many brain disorders. Zinc homeostasis and signaling are important mediators for a normal brain development and function, given that zinc deficiency was shown to result in cognitive and emotional deficits in animal models that might be associated with neurodevelopmental disorders. One underlying mechanism of the observed detrimental effects of zinc deficiency on the brain might be impaired proliferation and differentiation of stem cells participating in neurogenesis. Thus, to examine the molecular mechanisms regulating zinc metabolism and signaling in differentiating neurons, using a protocol for motor neuron differentiation, we characterized the expression of zinc homeostasis genes during neurogenesis using human induced pluripotent stem cells (hiPSCs) and evaluated the influence of altered zinc levels on the expression of zinc homeostasis genes, cell survival, cell fate, and neuronal function. Our results show that zinc transporters are highly regulated genes during neuronal differentiation and that low zinc levels are associated with decreased cell survival, altered neuronal differentiation, and, in particular, synaptic function. We conclude that zinc deficiency in a critical time window during brain development might influence brain function by modulating neuronal differentiation.
Address Institute for Anatomy and Cell Biology, Ulm University, 89081 Ulm, Germany; WG Molecular Analysis of Synaptopathies, Neurology Department, Neurocenter of Ulm University, 89081 Ulm, Germany
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 1687-5443 ISBN Medium
Area Expedition Conference
Notes PMID:27247802 Approved no
Call Number ref @ user @ Serial 95949
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