Alteration of nociceptive Schwann cells in a mouse model of high-fat diet induced diabetic peripheral neuropathy

Diabetic peripheral neuropathy (DPN) is characterized by progressive and symmetrical sensory abnormalities and constitutes one of the earliest and main complications of diabetes. DPN is characterized by heterogeneous sensory symptoms such as chronic pain, tingling, burning or loss of sensation. Nociceptive Schwann cells (nSCs), a recently identified subtypes of dermal Schwann cells support terminal nerve fibers in mouse skin and contribute to mechanical sensation and neuropathic pain. While terminal nerve fibers density is evaluated in DPN models, there is currently no data about nSCs number and integrity during the early stages of the disease. In the present study, we determined the quantitative differences in terminal nerve fiber density as well as nSCs number and cellular extensions between control and high-fat diet (HFD) induced diabetic mice presenting with a neuropathic phenotype. We also characterized L1CAM as a reliable and specific marker of nSCs, a cell type previously assessed by the expression of S100β and Sox10. Interestingly, we observed a decrease in intraepidermal nerve fiber density (IENFD) associated with a significant reduction of nSCs in the glabrous foot skin of neuropathic mice. Overall, this study identifies L1CAM as a new marker of nSCs and indicates that these cells are impacted in diabetic peripheral neuropathy.