Motor skills training-induced activation of descending pathways mediating cortical command to hindlimb motoneurons in experimental diabetic rats

Abstract

Diabetes disrupts the corticospinal tract (CST) system components that control hindlimb and trunk movement, resulting in weakness of the lower extremities. However, there is no information about a method to improve these disorders. This study aimed to investigate the rehabilitative effects of 2 weeks of aerobic training (AT) and complex motor skills training (ST) on motor disorders in streptozotocin-induced type 1 diabetic rats. In this study, electrophysiological mapping of the motor cortex showed that the diabetes mellitus (DM)-ST group had a larger motor cortical area compared to the DM-AT group and sedentary diabetic animals. Moreover, hand grip strength and rotarod latency increased in the DM-ST group; however, these two parameters did not change in the DM-AT group, as well as in control and sedentary diabetic rats. Furthermore, in the DM-ST group, cortical stimulation-induced and motor-evoked potentials were preserved after the interception of the CST; however, this potential disappeared after additional lesions were made on lateral funiculus, suggesting that their function extends to activating motor descending pathways other than the CST locating lateral funiculus. According to immunohistochemical analysis, the larger fibers present on the dorsal part of the lateral funiculus, which corresponds to the rubrospinal tract of the DM-ST group, expressed the phosphorylated growth-associated protein, 43 kD, which is a specific marker of axons with plastic changes. Additionally, electrical stimulation of the red nucleus revealed expansion of the hindlimb-responsible area and increased motor-evoked potentials of the hindlimb in the DM-ST group, suggesting a strengthening of synaptic connections between the red nucleus and spinal interneurons driving motoneurons. These results reveal that ST induces plastic changes in the rubrospinal tract in a diabetic model, which can compensate for diabetes by disrupting the CST system components that control the hindlimb. This finding suggests that ST can be a novel rehabilitation strategy to improve motor dysfunctions in diabetic patients.