TY - ABST

T1 - Investigation of function and structure of Corpus Callosum following a CRMP2 knockout in a Schizophrenia mouse model

T2 - Society for Neuroscience meeting 2022

AU - Midtgaard, Jens

AU - Grycel, K

AU - Xu, Z

AU - Hasselholt, S

AU - Nyengaard, J R

PY - 2022

Y1 - 2022

N2 - Myelination is an essential process to keep signal transduction and communication within the brain at an optimal level. There is evidence for impaired myelination in several neuropsychiatric disorders including Schizophrenia (SZ) (Ohtani et al., 2015). Collapsin Response Mediator Protein 2 (CRMP2) is one of the SZ risk-genes (Hensley et al., 2011). This project focuses on Central Nervous System demyelination as a component of SZ. We used a CRMP2 conditional knock out mouse (cKO) model to investigate myelin of the largest white matter structure, Corpus Callosum (CC). We looked at the function, structure and ultrastructure to elucidate which myelin parameters may be mostly affected. We investigated function of CC using multielectrode electrophysiology of compound action potentials(CAPs) (n = 4-9/group, P60-P90) in acute brain slices. Light microscopy was used to investigate structure, we measured the volume of CC and estimated the total number of oligodendrocytes (n = 6-7/group, P60-P90) with stereological methods. We examined the ultrastructure with 3D axonal and myelin reconstructions of image stacks acquired by Serial Block Face Scanning Electron Microscopy (SBEM),implementing an image-segmentation pipeline. Several parameters of Nodes of Ranvier (NR) (volume, length, diameter, axon diameter and myelin thickness) were manually quantified (n = 2/group, P60-P90). We saw indication of altered CAP signals and a reduction in CC volume, but not in the number of oligodendrocytes. Ultrastructural results suggest changes in NR structure in CRMP2-cKO animals. Morphometric analysis of full SBEM volumes are ongoing. Together our findings indicate that CRMP2 plays a role in white matter function in a SZ model. Both the function and structure of CC have been affected by the lack of CRMP2. Our project has implemented analysis methods to shed light on the role of myelin defects in SZ. The analytic pipelines can be used in future work on genetic models of neuropsychiatric disorders.Hensley, K., Venkova, K., Christov, A., Gunning, W., & Park, J. (2011). Collapsin Response Mediator Protein-2 : An Emerging Pathologic Feature and Therapeutic Target for Neurodisease Indications. MolecularNeurobiology, 43, 180-191. https://doi.org/10.1007/s12035-011-8166-4Ohtani, T., Bouix, S., Lyall, A. E., Hosokawa, T., Saito, Y., Melonakos, E., Westin, C. F., Seidman, L. J.,Goldstein, J., Mesholam-Gately, R., Petryshen, T., Wojcik, J., & Kubicki, M. (2015). Abnormal whitematter connections between medial frontal regions predict symptoms in patients with first episodeschizophrenia. Cortex, 71, 264-276. https://doi.org/10.1016/j.cortex.2015.05.028

AB - Myelination is an essential process to keep signal transduction and communication within the brain at an optimal level. There is evidence for impaired myelination in several neuropsychiatric disorders including Schizophrenia (SZ) (Ohtani et al., 2015). Collapsin Response Mediator Protein 2 (CRMP2) is one of the SZ risk-genes (Hensley et al., 2011). This project focuses on Central Nervous System demyelination as a component of SZ. We used a CRMP2 conditional knock out mouse (cKO) model to investigate myelin of the largest white matter structure, Corpus Callosum (CC). We looked at the function, structure and ultrastructure to elucidate which myelin parameters may be mostly affected. We investigated function of CC using multielectrode electrophysiology of compound action potentials(CAPs) (n = 4-9/group, P60-P90) in acute brain slices. Light microscopy was used to investigate structure, we measured the volume of CC and estimated the total number of oligodendrocytes (n = 6-7/group, P60-P90) with stereological methods. We examined the ultrastructure with 3D axonal and myelin reconstructions of image stacks acquired by Serial Block Face Scanning Electron Microscopy (SBEM),implementing an image-segmentation pipeline. Several parameters of Nodes of Ranvier (NR) (volume, length, diameter, axon diameter and myelin thickness) were manually quantified (n = 2/group, P60-P90). We saw indication of altered CAP signals and a reduction in CC volume, but not in the number of oligodendrocytes. Ultrastructural results suggest changes in NR structure in CRMP2-cKO animals. Morphometric analysis of full SBEM volumes are ongoing. Together our findings indicate that CRMP2 plays a role in white matter function in a SZ model. Both the function and structure of CC have been affected by the lack of CRMP2. Our project has implemented analysis methods to shed light on the role of myelin defects in SZ. The analytic pipelines can be used in future work on genetic models of neuropsychiatric disorders.Hensley, K., Venkova, K., Christov, A., Gunning, W., & Park, J. (2011). Collapsin Response Mediator Protein-2 : An Emerging Pathologic Feature and Therapeutic Target for Neurodisease Indications. MolecularNeurobiology, 43, 180-191. https://doi.org/10.1007/s12035-011-8166-4Ohtani, T., Bouix, S., Lyall, A. E., Hosokawa, T., Saito, Y., Melonakos, E., Westin, C. F., Seidman, L. J.,Goldstein, J., Mesholam-Gately, R., Petryshen, T., Wojcik, J., & Kubicki, M. (2015). Abnormal whitematter connections between medial frontal regions predict symptoms in patients with first episodeschizophrenia. Cortex, 71, 264-276. https://doi.org/10.1016/j.cortex.2015.05.028

M3 - Conference abstract for conference

SP - 411.16

ER -