Development of sensory neuropathy in streptozotocin-induced diabetic mice



Tatsufumi Murakami, Department of Neurology, Kawasaki Medical School,

577 Matsushima, Kurashiki,

Okayama 701-0192, Japan.

Tel: +81-86-462-1111; Fax: +81-86-462-1199; E-mail:


Diabetic polyneuropathy is a major complication of diabetes and the most common cause of peripheral neuropathy. Sensory-dominant neuropathy is the most common type. We previously used streptozotocin (STZ)-induced diabetic ddY mice with sensory neuropathy to evaluate the therapeutic effects of vascular endothelial growth factor and placental growth factor isoforms. In this study, to characterize the development of diabetic sensory neuropathy, electrophysiological, behavioral, and histopathological studies were performed in these diabetic mice. A significant difference in sensory conduction velocity in the tail nerve was observed between healthy and diabetic mice at 1 week after STZ injection. Diabetic mice developed hypoalgesia at 5 weeks after STZ injection. Axon area and myelin thickness of the myelinated fibers were increased in 17-week-old healthy mice compared with those in 8-week-old healthy mice. However, these increases were retarded in 17-week-old diabetic mice. In unmyelinated fibers, axon area was significantly reduced in 17-week-old diabetic mice compared with 8- and 17-week-old healthy mice. These findings suggest that both impaired maturation of myelinated fibers and atrophy of unmyelinated fibers simultaneously occur in the early stage of diabetes in these mice. Our mouse model may be useful for studying the pathogenesis of and therapies for diabetic sensory neuropathy.