Macrophage depletion restores the DRG microenvironment and prevents axon degeneration in bortezomib-induced neuropathy.

ABSTRACT: Peripheral neuropathy is a common and debilitating side effect of the chemotherapeutic bortezomib (BTZ). To explore the mechanisms underlying BTZ-induced neuropathy (BIPN), we developed a mouse model that replicates the route of administration and approximates the prolonged BTZ exposure experienced by patients. We find that male mice treated with BTZ experience more severe sensorimotor dysfunction and axon loss compared to females and observed similar results when analyzing human data. Using single cell RNA-sequencing, we reveal that BTZ significantly alters the dorsal root ganglia (DRG) microenvironment in mice, producing pronounced sex-specific changes in satellite glial cells (SGCs) in males and females and dysregulation of the extracellular matrix (ECM), particularly in males. These ch

SUBMITTER: Thomsen MB 

PROVIDER: S-EPMC11785175 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature