Direct Measurement of Fast Axonal Organelle Transport in Chronic Ethanol-Fed Rats

While indirect methods have been used, direct evaluation and measurement of the fast axonal transport system itself in chronic ethanolfed rats have not been carried out previously. We evaluated this system using analog and digital image enhancement of differential interference contrast optical images in real time to assess the effect of ethanol on fast intra-axonal organelle traffic in rat sural nerve. A radiolabeling method for evaluating fast axonal transport was used in similar animals to compare the indirect and direct techniques. Also, the concentration of organelles (mitochondria, large and small clear vesicles, dense vesicles, and membranous whorls) in the annulospiral sensory nerve endings of muscle spindles from a foot muscle (flexor digitorum brevis) of these same animals was quantitated from electron micrographs. Rats were fed an ethanol-containing liquid diet for one to five months. Three observations were made; (1) There was no statistically significant change in the mean organelle speed in the anterograde direction, but the mean organelle speed in the retrograde direction increased 11%, 9%, and 17% (statistically significant) at 3, 4, and 5 months of ethanol exposure, respectively. (2) Significant increases in organelle content of sensory nerve endings were seen at 2 and 3 months of intoxication. (3) Increases in organelle densities in terminals were transitory and returned to normal in the face of on-going ethanol administration. We conclude: (1) There is no permanent impairment of fast axonal organelle transport in this model after 5 months of exposure. (2) Sensory endings on muscle spindles show transitory increases in organelle density. (3) Retrograde speed increases may be a partial compensatory mechanism to help restore normal terminal organelle density. Both the return of sensory organelle content to normal and the increase in the number of retrograde organelles moving at the higher transport rates suggest the activation of compensatory mechanisms in the neuron early in the course of sustained ethanol intoxication.