Poor Motor-Function Recovery after Spinal Cord Injury in Anxiety-Model Mice with Phospholipase C-Related Catalytically Inactive Protein Type 1 Knockout

Taka Fujita, Gentaro Kumagai, Xizhe Liu, Kanichiro Wada, Toshihiro Tanaka, Hitoshi Kudo, Toru Asari, Tatsuhiro Fukutoku, Ayako Sasaki, Yohshiro Nitobe, Yoshikazu Nikaido, Ken Ichi Furukawa, Masato Hirata, Takashi Kanematsu, Shinya Ueno, Yasuyuki Ishibashi

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Abstract

Mice with a knockout of phospholipase C (PLC)-related inactive protein type 1 (PRIP1 -/- mice) display anxiety-like behavior and altered γ-aminobutyric acid (GABA) A -receptor pharmacology. Here, we examined associations between anxiety and motor-function recovery in PRIP1 -/- mice after a spinal cord injury (SCI) induced by a moderate contusion injury at the 10th thoracic level. Uninjured PRIP1 -/- mice showed less distance than wild-type (WT) mice in the center 25% in an open field test (OFT), indicating anxiety-like behavior. Anxiety behavior increased in both WT and PRIP1 -/- mice after SCI. WT and PRIP1 -/- mice were completely paralyzed on day 1 after SCI, but gradually recovered until reaching a plateau at ∼4 weeks. After SCI, the PRIP1 -/- mice had significantly greater motor dysfunction than the WT mice. In WT mice after SCI, the percentage of distance spent in the center 25% of the OFT was correlated with the OFT distance traveled and velocity, and with the reaction time in a plantar pressure-sensitivity mechanical test. In PRIP1 -/- mice after SCI, the percentage of distance spent in the center 25% of the OFT was correlated with the OFT distance traveled and with the latency to fall in the rotarod test. Six weeks after SCI, ionized calcium binding adaptor molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP) expressions were elevated at the lesion epicenter in PRIP1 -/- mice, and spinal cord atrophy and demyelination were more severe than in WT mice. The axonal fiber development was also decreased in PRIP1 -/- mice, consistent with the poor motor-function recovery after SCI in these mice.

Original languageEnglish
Pages (from-to)1379-1386
Number of pages8
JournalJournal of Neurotrauma
Volume35
Issue number12
DOIs
Publication statusPublished - Jun 15 2018
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Clinical Neurology

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  • Cite this

    Fujita, T., Kumagai, G., Liu, X., Wada, K., Tanaka, T., Kudo, H., Asari, T., Fukutoku, T., Sasaki, A., Nitobe, Y., Nikaido, Y., Furukawa, K. I., Hirata, M., Kanematsu, T., Ueno, S., & Ishibashi, Y. (2018). Poor Motor-Function Recovery after Spinal Cord Injury in Anxiety-Model Mice with Phospholipase C-Related Catalytically Inactive Protein Type 1 Knockout. Journal of Neurotrauma, 35(12), 1379-1386. https://doi.org/10.1089/neu.2017.5492