# Hyperglycemia Modulates mTOR Signaling and Myelin Protein Expression in Schwann Cells

## TL;DR

High blood sugar disrupts myelin production in Schwann cells by altering mTOR signaling, potentially contributing to diabetic nerve damage.

## Contribution

This study identifies mTOR signaling and myelin protein expression changes in Schwann cells under hyperglycemic conditions as potential mechanisms in diabetic neuropathy.

## Key findings

- Hyperglycemia significantly reduces myelin basic protein (MBP) expression in Schwann cells.
- High glucose levels impair mTOR activation, as indicated by reduced total and phosphorylated mTOR levels.
- These changes suggest a link between mTOR dysregulation and Schwann cell dysfunction in diabetic neuropathy.

## Abstract

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes, marked by Schwann cell dysfunction, demyelination, and impaired nerve regeneration. Although Schwann cells undergo phenotypic changes under hyperglycemic conditions, the underlying molecular mechanisms remain unclear. This study aimed to examine the effects of high glucose on Schwann cell phenotype and assess the involvement of the mTOR signaling pathway. Primary Schwann cells were isolated from rat sciatic nerves and cultured in media containing 5 mM (control), 25 mM, or 50 mM glucose for five days. Immunofluorescence staining and corrected total cell fluorescence (CTCF) analysis were used to evaluate expression of key markers: c-Jun, Krox-20, p75NTR, MBP, mTOR, phosphorylated mTOR (Ser2448), and AKR1B1. Among these, significant changes were observed in MBP (p = 0.002), total mTOR (p = 0.001), and phosphorylated mTOR (Ser2448) (p = 0.0179), indicating impaired mTOR activation and loss of myelin protein expression. Non-significant changes in the other markers are discussed as preliminary observations. These findings highlight mTOR dysregulation and impaired myelin protein expression as central features of Schwann cell responses to hyperglycemia, which may contribute to the development of DPN.