Progressive Anxiety-Like Behavior and Motor Dysfunction in a Murine Model of Spinal Ligament Ossification

Study Design: Longitudinal observational study using a murine model of spinal ligament ossification. Objective: To characterize temporal changes in motor, sensory, and anxiety-like behaviors in tiptoe walking (ttw) mice and to assess whether systemic biochemical or hematological alterations accompany these changes. Background: Chronic spinal cord compression, such as that caused by ossification of the posterior longitudinal ligament (OPLL), leads to progressive neurological dysfunction. However, its impact on anxiety-like behavior and sensory processing remains poorly understood. The ttw mouse develops progressive spinal ligament ossification beginning around eight weeks of age and serves as a relevant experimental model. Materials and Methods: Male ttw mice and age-matched C57BL/6J wild-type (WT) mice were evaluated every four weeks from 4 to 24 weeks of age. Motor function was assessed using the Basso Mouse Scale (BMS) and open field test (OFT). Anxiety-like behavior was quantified as the percentage of walking distance in the center 25% of the OFT arena (IC25%). Sensory function was evaluated using mechanical and thermal nociceptive tests. Blood samples collected at 8, 16, and 24 weeks were analyzed for biochemical and hematological parameters. Results: ttw mice showed a significant reduction in BMS scores from eight weeks of age, whereas reductions in locomotor activity and IC25% values became evident from 12 weeks onward ( P < 0.05). At four weeks, ttw mice traveled a greater total distance than WT mice, followed by a progressive decline at later time points. Thermal withdrawal latency was prolonged at 20 and 24 weeks, indicating sensory dulling. IC25% correlated with BMS at 12 weeks (R = 0.586, P = 0.035) but not thereafter. No consistent differences were observed in blood biochemical or hematological parameters. Conclusions: Progressive spinal ligament ossification in ttw mice leads to motor impairment and anxiety-like behavior that become dissociated as chronic spinal cord compression advances. Level of Evidence: Level V.