Alterations in the neural circuits from peripheral afferents to the spinal cord: possible implications for diabetic polyneuropathy in streptozotocin-induced type 1 diabetic rats

Zhen-Zhen Kou, Chun-Yu Li, Jia-Chen Hu, Jun-Bin Yin, Dong-Liang Zhang, Yong-Hui Liao, Zhen-Yu Wu, Tan Ding, Juan Qu, Hui Li, Yun-Qing Li

Diabetic polyneuropathy (DPN) presents as a wide variety of sensorimotor symptoms and affects approximately 50% of diabetic patients. Changes in the neural circuits may occur in the early stages in diabetes and are implicated in the development of DPN. Therefore, we aimed to detect changes in the expression of isolectin B4 (IB4, the marker for nonpeptidergic unmyelinated fibers and their cell bodies) and calcitonin gene-related peptide (CGRP, the marker for peptidergic fibers and their cell bodies) in the dorsal root ganglion (DRG) and spinal cord of streptozotocin (STZ)-induced type 1 diabetic rats showing alterations in sensory and motor function. We also used cholera toxin B subunit (CTB) to show the morphological changes of the myelinated fibers and motor neurons. STZ-induced diabetic rats exhibited hyperglycemia, decreased body weight gain, mechanical allodynia and impaired locomotor activity. In the DRG and spinal dorsal horn, IB4-labeled structures decreased, but both CGRP immunostaining and CTB labeling increased from day 14 to day 28 in diabetic rats. In spinal ventral horn, CTB labeling decreased in motor neurons in diabetic rats. Treatment with intrathecal injection of insulin at the early stages of DPN could alleviate mechanical allodynia and impaired locomotor activity in diabetic rats. The results suggest that the alterations of the neural circuits between spinal nerve and spinal cord via the DRG and ventral root might be involved in DPN.