Objective
Epidemiological data link cassava consumption and konzo, an upper motoneurone disease characterized by spastic paraparesis. Cassava contains gluconitriles, mostly linamarin and the incidence of konzo correlates with urine concentrations of this compound. Trans-crotonitrile (TCN), an industrial nitrile, causes degeneration of the inferior olive, source of climbing fibres (CFs) to the cerebellum. Pilot studies have found that cerebellar CF field potentials are reduced in size after exposure to TCN or the metabolite of linamarin, acetonecyanohydrin (ACH). Hypothesis : Nitriles in cassava (linamarin, ACH, methyl-ethyl-ketonecyanohydrin, MEKCH) cause konzo through their neurotoxic action on the olive.Objectives : -Study transmission in CF and other sensorimotor pathways in anaesthetized rats exposed to linamarin, ACH or MEKCH. Prediction : effects of nitriles will be selective to the CF system.-Monitor changes in CF function and motor behavior in awake rats. Prediction : changes in CF excitability will be related to motor deficits.-Histological study of CNS. Prediction : functional deficits will be related to olivary degeneration.-Study spinal reflexes and muscle tone. Prediction : these will be increased as observed in konzo patients. The project will therefore contribute to the understanding of konzo and other spastic paraparesis syndromes, and of the role of the inferior olive in motor control. The applicant will learn specialized electrophysiological techniques and gain insights into the functional organization of central pathways critical in motor control.
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Programme(s)
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Coordinator
BS8 1TD BRISTOL, CLIFTON
United Kingdom
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.