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Disorganization of Oligodendrocyte Development in the Layer II/III of the Sensorimotor Cortex Causes Motor Coordination Dysfunction in a Model of White Matter Injury in Neonatal Rats

Neurochemical Research volume 43, pages 136–146 (2018)Cite this article

Abstract

We previously established neonatal white matter injury (WMI) model rat that is made by right common carotid artery dissection at postnatal day 3, followed by 6% hypoxia for 60 min. This model has fewer oligodendrocyte progenitor cells and reduced myelin basic protein (MBP) positive areas in the sensorimotor cortex, but shows no apparent neuronal loss. However, how motor deficits are induced in this model is unclear. To elucidate the relationship between myelination disturbance and concomitant motor deficits, we first performed motor function tests (gait analysis, grip test, horizontal ladder test) and then analyzed myelination patterns in the sensorimotor cortex using transmission electron microscopy (TEM) and Contactin associated protein 1 (Caspr) staining in the neonatal WMI rats in adulthood. Behavioral tests revealed imbalanced motor coordination in this model. Motor deficit scores were higher in the neonatal WMI model, while hindlimb ladder stepping scores and forelimb grasping force were comparable to controls. Prolonged forelimb swing times and decreased hindlimb paw angles on the injured side were revealed by gait analysis. TEM revealed no change in myelinated axon number and the area g-ratio in the layer II/III of the cortex. Electromyographical durations and latencies in the gluteus maximus in response to electrical stimulation of the brain area were unchanged in the model. Caspr staining revealed fewer positive dots in layers II/III of the WMI cortex, indicating fewer and/or longer myelin sheath. These data suggest that disorganization of oligodendrocyte development in layers II/III of the sensorimotor cortex relates to imbalanced motor coordination in the neonatal WMI model rat.

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Acknowledgements

This study was supported by Grants-in-Aid for Scientific Research in priority area (C) (# 26430020 to HH, # 16K10100 to SM), and young area (B) (# 26860851 to SM), and a Grant-in-Aid for Research Activity Start-up (# 15H06538 to YU) from the Japan Society for the Promotion of Science (JSPS). This study was also supported by a Grant-in-Aid for Scientific Research on Innovative Areas (Adaptive Circuit Shift) to H.H. We thank Hiroshi Takase in Core Laboratory of Nagoya City University Graduate School to support TEM study. We thank Edanz Group Ltd. for providing language help in editing this manuscript.

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Affiliations

  1. Departments of Neurophysiology and Brain Science, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan

    Yoshitomo Ueda, Sachiyo Misumi, Mina Suzuki, Shino Ogawa, Ruriko Nishigaki, Akimasa Ishida, Cha-Gyun Jung & Hideki Hida

  2. Departments of Obstetrics and Gynecology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan

    Shino Ogawa

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  1. Yoshitomo Ueda
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  2. Sachiyo Misumi
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  3. Mina Suzuki
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Correspondence to Hideki Hida.

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Supplementary material 1 (TIF 2931 KB)

Supplementary Fig. 1 Comparison between groups of the gait indices for each paw. We compared undamaged shams (sham operation followed by normoxia), controls (sham operation followed by 6% hypoxia), and WMI (right CCA occlusion followed by 6% hypoxia) groups. † p < 0.05 by one-way ANOVA and post hoc Tukey-Kramer test

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Ueda, Y., Misumi, S., Suzuki, M. et al. Disorganization of Oligodendrocyte Development in the Layer II/III of the Sensorimotor Cortex Causes Motor Coordination Dysfunction in a Model of White Matter Injury in Neonatal Rats. Neurochem Res 43, 136–146 (2018). https://doi.org/10.1007/s11064-017-2352-3

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  • DOI: https://doi.org/10.1007/s11064-017-2352-3

Keywords

  • Hypoxia–ischemia in premature infants
  • White matter injury
  • Gait analysis
  • Transmission electron microscopy
  • Caspr staining