CRMP2 conditional knockout changes axonal function and ultrastructure of axons in mice corpus callosum

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  • Katarzyna Grycel
  • Nick Y. Larsen
  • Yinghang Feng
  • Qvortrup, Klaus
  • Poul Henning Jensen
  • Mishal Fayyaz
  • Malene G. Madsen
  • Midtgaard, Jens
  • Zhiheng Xu
  • Stine Hasselholt
  • Jens R. Nyengaard

Collapsin response mediator protein 2 (CRMP2) is a member of a protein family, which is highly involved in neurodevelopment, but most of its members become heavily downregulated in adulthood. CRMP2 is an important factor in neuronal polarization, axonal formation and growth cone collapse. The protein remains expressed in adulthood, but is more region specific. CRMP2 is present in adult corpus callosum (CC) and in plastic areas like prefrontal cortex and hippocampus. CRMP2 has been implicated as one of the risk-genes for Schizophrenia (SZ). Here, a CRMP2 conditional knockout (CRMP2-cKO) mouse was used as a model of SZ to investigate how it could affect the white matter and therefore brain connectivity. Multielectrode electrophysiology (MEA) was used to study the function of corpus callosum showing an increase in conduction velocity (CV) measured as Compound Action Potentials (CAPs) in acute brain slices. Light- and electron-microscopy, specifically Serial Block-face Scanning Electron Microscopy (SBF-SEM), methods were used to study the structure of CC in CRMP2-cKO mice. A decrease in CC volume of CRMP2-cKO mice as compared to controls was observed. No differences were found in numbers nor in the size of CC oligodendrocytes (OLs). Similarly, no differences were found in myelin thickness or in node of Ranvier (NR) structure. In contrast, abnormally smaller axons were measured in the CRMP2-cKO mice. Using these state-of-the-art methods it was possible to shed light on specific parts of the dysconnectivity aspect of deletion of CRMP2 related to SZ and add details to previous findings helping further understanding the disease. This paper substantiates the white matter changes in the absence of CRMP2 and ties it to the role it plays in this complex disorder.

Original languageEnglish
Article number103882
JournalMolecular and Cellular Neuroscience
Number of pages11
Publication statusPublished - 2023

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© 2023 The Authors

    Research areas

  • CRMP2, Dysconnectivity, Mouse model, Schizophrenia, White matter

ID: 361829740