@unpublished{SchaeferJanzenBakircietal.2019,
  author    = {Schaefer, Natascha and Janzen, Dieter and Bakirci, Ezgi and Hrynevich, Andrei and Dalton, Paul D. and Villmann, Carmen},
  title     = {3D Electrophysiological Measurements on Cells Embedded within Fiber-Reinforced Matrigel},
  series = {Advanced Healthcare Materials},
  journal   = {Advanced Healthcare Materials},
  doi       = {10.1002/adhm.201801226},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-244194},
  year      = {2019},
  abstract  = {2D electrophysiology is often used to determine the electrical properties of neurons, while in the brain, neurons form extensive 3D networks. Thus, performing electrophysiology in a 3D environment provides a closer situation to the physiological condition and serves as a useful tool for various applications in the field of neuroscience. In this study, we established 3D electrophysiology within a fiber-reinforced matrix to enable fast readouts from transfected cells, which are often used as model systems for 2D electrophysiology. Using melt electrowriting (MEW) of scaffolds to reinforce Matrigel, we performed 3D electrophysiology on a glycine receptor-transfected Ltk-11 mouse fibroblast cell line. The glycine receptor is an inhibitory ion channel associated when mutated with impaired neuromotor behaviour. The average thickness of the MEW scaffold was 141.4 ± 5.7µm, using 9.7 ± 0.2µm diameter fibers, and square pore spacings of 100 µm, 200 µm and 400 µm. We demonstrate, for the first time, the electrophysiological characterization of glycine receptor-transfected cells with respect to agonist efficacy and potency in a 3D matrix. With the MEW scaffold reinforcement not interfering with the electrophysiology measurement, this approach can now be further adapted and developed for different kinds of neuronal cultures to study and understand pathological mechanisms under disease conditions.},
  language  = {en}
}
@unpublished{BrennerZinkWitzingeretal.2024,
  author    = {Brenner, Marian and Zink, Christoph and Witzinger, Linda and Keller, Angelika and Hadamek, Kerstin and Bothe, Sebastian and Neuenschwander, Martin and Villmann, Carmen and von Kries, Jens Peter and Schindelin, Hermann and Jeanclos, Elisabeth and Gohla, Antje},
  title     = {7,8-Dihydroxyflavone is a direct inhibitor of pyridoxal phosphatase},
  series = {eLife},
  journal   = {eLife},
  doi       = {10.7554/eLife.93094.2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350446},
  year      = {2024},
  abstract  = {Vitamin B6 deficiency has been linked to cognitive impairment in human brain disorders for decades. Still, the molecular mechanisms linking vitamin B6 to these pathologies remain poorly understood, and whether vitamin B6 supplementation improves cognition is unclear as well. Pyridoxal phosphatase (PDXP), an enzyme that controls levels of pyridoxal 5'-phosphate (PLP), the co-enzymatically active form of vitamin B6, may represent an alternative therapeutic entry point into vitamin B6-associated pathologies. However, pharmacological PDXP inhibitors to test this concept are lacking. We now identify a PDXP and age-dependent decline of PLP levels in the murine hippocampus that provides a rationale for the development of PDXP inhibitors. Using a combination of small molecule screening, protein crystallography and biolayer interferometry, we discover and analyze 7,8-dihydroxyflavone (7,8-DHF) as a direct and potent PDXP inhibitor. 7,8-DHF binds and reversibly inhibits PDXP with low micromolar affinity and sub-micromolar potency. In mouse hippocampal neurons, 7,8-DHF increases PLP in a PDXP-dependent manner. These findings validate PDXP as a druggable target. Of note, 7,8-DHF is a well-studied molecule in brain disorder models, although its mechanism of action is actively debated. Our discovery of 7,8-DHF as a PDXP inhibitor offers novel mechanistic insights into the controversy surrounding 7,8-DHF-mediated effects in the brain.},
  language  = {en}
}