Poor Motor-Function Recovery After Spinal Cord Injury In Anxiety-Model Mice With Phospholipase C-Related Catalytically Inactive Protein Type 1 Knockout

Mice with a knockout of phospholipase C (PLC)-related inactive protein type 1 (PRIP1(-/-) mice) display anxiety-like behavior and altered -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 similar to 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.