@phdthesis{Samtleben2014,
  author    = {Samtleben, Samira},
  title     = {Investigation of homeostatic calcium fluxes in hippocampal neurons by means of targeted-esterase induced dye loading (TED)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-110332},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2014},
  abstract  = {Calcium ions can activate intracellular signalling cascades that control key functions in all types of neurons. These functions include neuronal excitability and excitation, synaptic plasticity, cell migration, transmitter release, gene transcription, and apoptosis. The major intracellular neuronal store for calcium is the endoplasmic reticulum (ER), a continuous and dynamic, membranous organelle that extends through all parts of neurons, from axons to dendrites. The calcium concentration in the ER is appr. one thousand fold higher than in the cytosol and this calcium gradient is built up by the sarco-/endoplasmic reticulum calcium ATPase (SERCA) pump that pumps calcium from the cytosol into the ER. Despite detailed knowledge about various induced calcium signals within neurons, it was still elusive, how resting neurons maintain their ER calcium content at rest. In order to shed light on the calcium homeostasis at rest, the targeted-esterase induced dye loading (TED) technique was improved. TED allows the direct and non-disruptive visualization of ER calcium in presence of extracellular calcium, thus enabling to visualize the dynamic flow of ER calcium. TED is based on the overexpression of an ER-targeted mouse carboxylesterase. Inside the ER the carboxylesterase cleaves the acetoxymethyl ester calcium dye Fluo5N, AM, thereby converting this dye into a calcium sensitive, low-affinity, cell membrane impermeable calcium indicator that is trapped in the ER. When bound to calcium ions and excited by fluorescent light, its fluorescence intensity increases one hundredfold compared to the calcium-free state. It was observed that calcium withdrawal from resting neurons led to a rapid loss of calcium from both the ER and the cytosol, which recovered upon calcium re-addition. It was concluded that a strong calcium influx and efflux must exist under resting conditions that maintain a constant calcium concentration in neurons at rest. TED calcium imaging could visualize this resting calcium influx event. When the inhibitor of store-operated calcium entry (SOCE), SKF-96365, was acutely added to neurons an immediate decline in ER calcium levels was observed, whereas cytosolic calcium levels remained constant. Based on these findings, a novel calcium homeostasis model is proposed in which a strong SOCE-like calcium influx and a corresponding calcium efflux maintain the ER calcium levels at rest. These fluxes are adapted to disturbances in order to maintain a constant calcium level in resting neurons. This study visualizes for the first time the resting calcium flow into the ER. The calcium enters the neurons via a store-operated calcium entry-like mechanism, a form of calcium influx that was thought to be induced by signalling events.},
  subject      = {Calciumhom{\"o}ostase},
  language  = {en}
}
@article{SchmittTatschVollhardtetal.2022,
  author    = {Schmitt, Andrea and Tatsch, Laura and Vollhardt, Alisa and Schneider-Axmann, Thomas and Raabe, Florian J. and Roell, Lukas and Heinsen, Helmut and Hof, Patrick R. and Falkai, Peter and Schmitz, Christoph},
  title     = {Decreased oligodendrocyte number in hippocampal subfield CA4 in schizophrenia: a replication study},
  series = {Cells},
  volume    = {11},
  journal   = {Cells},
  number    = {20},
  issn      = {2073-4409},
  doi       = {10.3390/cells11203242},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-290360},
  year      = {2022},
  abstract  = {Hippocampus-related cognitive deficits in working and verbal memory are frequent in schizophrenia, and hippocampal volume loss, particularly in the cornu ammonis (CA) subregions, was shown by magnetic resonance imaging studies. However, the underlying cellular alterations remain elusive. By using unbiased design-based stereology, we reported a reduction in oligodendrocyte number in CA4 in schizophrenia and of granular neurons in the dentate gyrus (DG). Here, we aimed to replicate these findings in an independent sample. We used a stereological approach to investigate the numbers and densities of neurons, oligodendrocytes, and astrocytes in CA4 and of granular neurons in the DG of left and right hemispheres in 11 brains from men with schizophrenia and 11 brains from age- and sex-matched healthy controls. In schizophrenia, a decreased number and density of oligodendrocytes was detected in the left and right CA4, whereas mean volumes of CA4 and the DG and the numbers and density of neurons, astrocytes, and granular neurons were not different in patients and controls, even after adjustment of variables because of positive correlations with postmortem interval and age. Our results replicate the previously described decrease in oligodendrocytes bilaterally in CA4 in schizophrenia and point to a deficit in oligodendrocyte maturation or a loss of mature oligodendrocytes. These changes result in impaired myelination and neuronal decoupling, both of which are linked to altered functional connectivity and subsequent cognitive dysfunction in schizophrenia.},
  language  = {en}
}