Morphophysiologic characterization of peripheral neuropathy in zinc-deficient guinea pigs.

Zinc-deficient guinea pigs develop a peripheral neuropathy characterized by abnormal posture and gait, hyperesthesia, slowed motor nerve conduction velocity (MNCV), and decreased sciatic nerve Na,K-ATPase activity. This study was designed to further investigate longitudinally the morphophysiologic features of the neuropathy. Weanling guinea pigs were fed a low-zinc (<1 mg/kg) diet ad libitum (-ZnAL), an adequate-zinc (100 mg/kg) diet ad libitum (+ZnAL), or the adequate diet restricted in intake ((+ZnRF). Electrophysiologic, morphologic, and biochemical parameters of peripheral nerves were examined at 2.5, 4.0, and 5.5 weeks. Serum zinc was significantly lower by 2.5 weeks and growth rate reduced by 4 weeks in -ZnAL animals. Postural abnormalities were first obvious at 4 weeks, although MNCVs were significantly slower in zinc-deficient animals at all time intervals. The conduction of sensory impulses, as measured by spinal cord somatosensory evoked potentials (sSSEP), was significantly slower in the -ZnAL animals at 5.5 weeks. Examination of teased preparations and histologic sections of sciatic nerves at 5.5 weeks revealed no degenerative lesions or differences in density of myelinated fibers (MF). The size frequency distribution of MF in all groups was unimodal, with a trend toward smaller myelinated nerve fibers in -ZnAL and +ZnRF animals. Sciatic nerve Na,K-ATPase activity in the -ZnAL animals was significantly reduced after 4 weeks of zinc deprivation. At 5.5 weeks, nerve concentrations of myo-inositol, glucose, fructose, and sorbitol were significantly decreased in -ZnAL animals compared with the +ZnRF and +ZnAL controls. The peripheral neuropathy associated with acute zinc deficiency is a parenchymatous axonal disorder characterized by slowed motor and sensory nerve impulse conduction and reduction in nerve Na,K-ATPase activity and nerve concentrations of simple sugars and their metabolites.