Trehalose suppresses DPN-induced neuron apoptosis by protecting mitochondrial function from oxidative stress. Myelin-related genes are involved in this process.

Highlights

Type 1 diabetes (T1DM) affects approximately 1 in 500 children. Diabetic peripheral neuropathy (DPN) is the most common form of peripheral neuropathy in diabetes and is a significant risk factor for serious pathological change. It is difficult and costly to treat DPN and although there have been several pivotal trials. The development of new drugs to treat DPN remains a high priority. Trehalose is a naturally occurring disaccharide, which is indicated to prevent maternal type 1 diabetes-induced neural tube defects. Thus, the primary aim of this study is to determine whether trehalose ameliorates DPN-induced sciatic nerve injury in TIDM. To establish a T1DM mouse model, wild-type (WT) male C57BL/6 J mice were injected with streptozotocin (STZ). WT mice, T1DM mice, and mice fed with trehalose were assayed for myelin-related gene expression and with behavioral tests. To mimic high glucose in vivo, Schwann cells were cultured under high glucose conditions with or without trehalose. In addition, oxidative damage, apoptosis, and mitochondrial translocation of the pro-apoptotic B-cell lymphoma-2 (Bcl-2) family members were assessed in Schwann cells. Results showed that treatment by trehalose prevented DPN and preserved diabetes-decreased expression of myelin-related genes in T1DM mice. Furthermore, trehalose abolished diabetes-suppressed regeneration of the sciatic nerve. More importantly, trehalose suppressed high glucose-induced oxidative damage and apoptosis in Schwann cells. In summary, trehalose ameliorates DPN-induced sciatic nerve injury in T1DM by preventing apoptosis, which makes it a promising candidate for the treatment of DPN.