Date of Award
Doctor of Philosophy (PhD)
Mechanosensory transduction changes both during development and after the application of vincristine, a neurotoxic agent. Specifically, cutaneous sensitivity mediated by Type I slowly adapting cutaneous mechanoreceptors (touch domes) changes over the course of development in two ways. The first is a reduction in the density of touch domes in the skin from birth to adulthood. The second mechanism involves an increase in threshold to mechanical stimulation from birth to old age. In control adult animals, administration of the neurotoxic drug vincristine increased mechanosensory threshold within 24 hours after treatment. This raised threshold was maintained for two weeks but there was a return to control values by three weeks post-treatment. Measurements of response latency indicated that the rise in receptor threshold could occur without impulse propagation being impaired in the axon. Both the morphological and physiological state of the axon twenty-four hours after vincristine treatment indicated that vincristine modified sensory transduction at the level of the touch domes or of the fine nerve terminals abutting it. Vincristine may have produced the temporary high threshold state of the receptor by direct action on the receptor or indirectly by interfering with axoplasmic flow. If the latter is the case, this observation provides indirect evidence for the existence of a functional connection between the flow of trophic factors in the nerve fibres supplying touch domes and the mechanosensory transduction process in the receptor. Possible mechanisms for the changes observed in receptor properties during ageing and drug treatment are presented. It is proposed that during ageing a functional deafferentation occurs; the implications of this proposed process on the ageing nervous system are discussed. It is suggested that similar mechanisms may underlie threshold changes seen during ageing and after the administration of vincristine.
Leon, Judith Merer, "NORMAL AND DISORDERED FUNCTION IN A MAMMALIAN TOUCH RECEPTOR" (1982). Open Access Dissertations and Theses. Paper 3150.