Histopathological and Behavioral Assessment of Toxin-Produced Cerebellar Lesion: A Potent Model for Cell Transplantation Studies in The Cerebellum

OBJECTIVE: The cerebellum is a key structure involved in coordinated motor planning, cognition, learning and memory functions. This study presents a permanent model of a toxin produced cerebellar lesion characterized according to contemporary motor and cognitive abnormalities. MATERIALS AND METHODS: In this experimental study, slow administration of quinolinic acid (QA, 5 µl of 200 µmol, 1 µl/minute) in the right cerebellar hemisphere (lobule VI) caused noticeable motor and cognitive disturbances along with cellular degeneration in all treated animals. We assessed behavioral and histopathological studies over ten weeks after QA treatment. The data were analyzed with ANOVA and the student’s t test. RESULTS: The QA treated group showed marked motor learning deficits on the rotating rod test (p=0.0001), locomotor asymmetry on the cylinder test (p=0.0001), dysmetria on the beam balance test (p=0.0001), abnormalities in neuromuscular strength on the hang wire test (p=0.0001), spatial memory deficits in the Morris water maze (MWM, p=0.001) and fear conditioned memory on the passive avoidance test (p=0.01) over a ten-week period compared with the control animals. Histopathological analysis showed loss of Purkinje cells (p=0.001) and granular cell density (p=0.0001) in the lesioned hemisphere of the cerebellum. CONCLUSION: Results of the present study show that QA can remove numerous cells which respond to this toxin in hemispheric lobule VI and thus provide a potential model for functional and cell-based studies.