Changes in axon size and slow axonal transport are related in experimental diabetic neuropathy

In the sciatic system of rats with streptozocin (SZ)-induced diabetes, delay of axonal transport of neurofilament (NF) proteins, tubulin, and other proteins is associated with a change in axonal caliber, which increases by 40% in lumbar motor roots and decreases by 36% in tibial nerves. Since in large myelinated axons caliber is a function of the number of NF, which, in turn, is regulated by axonal transport, we studied the correlation of the number of NF and microtubules (MT) with axonal cross-sectional area in the sciatic system of SZ-treated rats to investigate whether the changes in caliber could be attributed to the impairment of transport. Despite the changes in cross-sectional area, diabetic axons in both proximal motor roots and distal tibial nerves maintained the ratios of number of NF and MT to cross-sectional area found in controls. Our findings suggest that, in rats with SZ-induced diabetes, the proximal and distal alterations of axonal caliber are an adjustment to the change in number of NF and/or MT that results from the impairment of the slow axonal transport.