SPONTANEOUS AGE-RELATED PERIPHERAL NEUROPATHY IN B6C3F1 MICE

Abstract

Peripheral neuropathy, which accompanies aging, occurs during the long-term rearing of laboratory animas. The present study set out to delineate the clinical and functional features of this neuropathy. A total of 2000 B6C3F1 female mice, in groups of 5 to 20 mice, were sacrificed and autopsied each week beginning at 5 weeks and continuing to 130 weeks of age. Examination for histopathologic changes was conducted on the dorsal nerve roots, sciatic nerves, peroneal nerves, tibial nerves, plantar nerves and brachial nerve plexuses. At 90 weeks of age or later, peripheral neuropathy, characterized by axonal degeneration and Schwann cell proliferation, were observed mainly in the sciatic nerves, brachial nerve plexus and peroneal nerves. These spontaneous age-related nerve lesions appeared in all animals by 100 weeks of age in all nerves, and increased with increasing age. The nerve lesions were most prominent in the distal sciatic nerve. The rectal and hind-limb surface temperatures, motor nerve conduction velocity, blood glucose and HbA_1c decreased with increasing age. Elevation of sorbitol contents in sciatic nerves and reduction of myo-inositol levels were also detected in 120-week-old mice. However, except for blood glycemic parameters, no correlation with peripheral nerve lesions could be demonstrated. Spontaneous hypoglycemia(<40 mg / dL)persisted throughout the day in a small percentage(<5%)of animals aged 80 weeks or more; these animals had extensive lesions in the peripheral nerves and showed decreased plasma levels of HbA_1c and frucutosamines and increased plasma levels of ketones. These results suggest that spontaneous peripheral nerve disorders which accompany aging might worsen if spontaneous age-related hypoglycemia is also present. Such age-related changes must be taken into consideration in experimental studies performed on mice of this age.