Rodent Experimental Model of Konzo: Characterization of Motor Impairment and Neurodegeneration after Cassava Neurotoxicity in the Rat

Abstract

Konzo is a motor neuron neurodegenerative disease caused by bitter cassava toxicity that presents as a non-progressive spastic paraparesis. The ability of bitter cassava to produce behavioural and structural changes in adult rat nervous system was examined. Twenty five rats were used for this study, and pruned to 20 after consistent baseline performance was achieved (n=20; control=5, cassava chow=15). The rats were switched to a cassava diet for another 5 weeks (n=15). After the cassava consumption period, 5 rats underwent rehabilitation training three times a week and their performance tested once in a week for 5 weeks. Quantitative and qualitative assessments using a reaching movement scale and reach-to-grasp success rate were respectively carried out. Animals subjected to cassava toxicity performed significantly worse than the controls when determining the success rate in a reach-to-grasp experiment (baseline=69.8%, cassava diet=21.4%, post-cassava diet =48.9%). The various movement of the rat was analysed using ANOVA and there was significant difference (p < 0.05) in the performance. The rats couldn’t pronate, grasp, withdraw or open the digits properly when fed with cassava diet. Histology showed neuropathological damages on the motor cortex, less neurons in the motor neuron pool of the spinal cord and disruption of pyramidal layer of the hippocampus when rats were given bitter cassava. Immunofluorescence stain shows motor neurons and numerous choline acetyltransferase (ChAT+) processes and some C-boutons. There are behavioural evidence and neuropathological changes in the motor cortex and ventral horn of the spinal cord that may underlie movement impairments in rats fed with bitter cassava.