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A novel NMDA receptor test model based on hiPSC-derived neural cells

  • Paul Disse ORCID logo EMAIL logo , Isabel Aymanns ORCID logo , Nadine Ritter ORCID logo , Stefan Peischard , Lisanne Korn , Heinz Wiendl , Matthias Pawlowski , Stjepana Kovac , Sven G. Meuth ORCID logo , Thomas Budde ORCID logo , Nathalie Strutz-Seebohm , Bernhard Wünsch ORCID logo and Guiscard Seebohm ORCID logo
Published/Copyright: January 12, 2023
Biological Chemistry
From the journal Biological Chemistry Volume 404 Issue 4

Abstract

N-Methyl-D-aspartate receptors (NMDARs) are central for learning and information processing in the brain. Dysfunction of NMDARs can play a key role in the pathogenesis of neurodegeneration and drug addiction. The development of selective NMDAR modulators represents a promising strategy to target these diseases. Among such modulating compounds are ifenprodil and its 3-benzazepine derivatives. Classically, the effects of these NMDAR modulators have been tested by techniques like two-electrode voltage clamp (TEVC), patch clamp, or fluorescence-based assays. However, testing their functional effects in complex human systems requires more advanced approaches. Here, we established a human induced pluripotent stem cell-derived (hiPSC-derived) neural cell system and proved its eligibility as a test system for investigating NMDAR modulators and pharmaceutical effects on human neurons.

Keywords: GluN2B; glutamatergic neurons; human stem cells; neurology; NMDAR; pharmacology
Corresponding author: Paul Disse, Institut für Genetik von Herzerkrankungen (IfGH), Zelluläre Elektrophysiologie, Universitätsklinikum Münster, D-48149 Münster, Germany; and Chembion, GRK 2515, Westfälische Wilhelms-Universität Münster, D-48149 Münster, Germany; E-mail:

Funding source: Deutsche Forschungsgemeinschaft

Award Identifier / Grant number: GRK2515

Acknowledgments

We thank Anne Humberg for her excellent technical assistance.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: This work was supported by the Research Training Group “Chemical biology of ion channels (Chembion)” funded by the Deutsche Forschungsgemeinschaft (DFG) and the MedK Münster, which is gratefully acknowledged.

  3. Conflict of interest statement: The authors declare to have no competing interests.

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Supplementary Material

This article contains Supplementary material (https://doi.org/10.1515/hsz-2022-0216).

Received: 2022-06-30
Accepted: 2022-12-12
Published Online: 2023-01-12
Published in Print: 2023-03-28

© 2022 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Highlight: Chemical Biology of Ion Channels
  3. Highlight: chemical biology of ion channels
  4. The second PI(3,5)P2 binding site in the S0 helix of KCNQ1 stabilizes PIP2-at the primary PI1 site with potential consequences on intermediate-to-open state transition
  5. In vitro ADME characterization of a very potent 3-acylamino-2-aminopropionic acid-derived GluN2C-NMDA receptor agonist and its ester prodrugs
  6. A novel NMDA receptor test model based on hiPSC-derived neural cells
  7. Chemical, pharmacodynamic and pharmacokinetic characterization of the GluN2B receptor antagonist 3-(4-phenylbutyl)-2,3,4,5-tetrahydro-1H-3-benzazepine-1,7-diol – starting point for PET tracer development
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  11. The role of the Na+/Ca2+-exchanger (NCX) in cancer-associated fibroblasts
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https://doi.org/10.1515/hsz-2022-0216
Keywords for this article
GluN2B; glutamatergic neurons; human stem cells; neurology; NMDAR; pharmacology

Articles in the same Issue

  1. Frontmatter
  2. Highlight: Chemical Biology of Ion Channels
  3. Highlight: chemical biology of ion channels
  4. The second PI(3,5)P2 binding site in the S0 helix of KCNQ1 stabilizes PIP2-at the primary PI1 site with potential consequences on intermediate-to-open state transition
  5. In vitro ADME characterization of a very potent 3-acylamino-2-aminopropionic acid-derived GluN2C-NMDA receptor agonist and its ester prodrugs
  6. A novel NMDA receptor test model based on hiPSC-derived neural cells
  7. Chemical, pharmacodynamic and pharmacokinetic characterization of the GluN2B receptor antagonist 3-(4-phenylbutyl)-2,3,4,5-tetrahydro-1H-3-benzazepine-1,7-diol – starting point for PET tracer development
  8. Characterization of Kv1.2-mediated outward current in TRIP8b-deficient mice
  9. Influence of inflammatory processes on thalamocortical activity
  10. NMDA receptors – regulatory function and pathophysiological significance for pancreatic beta cells
  11. The role of the Na+/Ca2+-exchanger (NCX) in cancer-associated fibroblasts
  12. Pancreatic KCa3.1 channels in health and disease
  13. Validation of TREK1 ion channel activators as an immunomodulatory and neuroprotective strategy in neuroinflammation
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