Schwann cell release of p11 induces sensory neuron hyperactivity in Fabry disease. bioRxiv 2023 May 28
Date
06/09/2023Pubmed ID
37292928Pubmed Central ID
PMC10245981DOI
10.1101/2023.05.26.542493Abstract
Patients with Fabry disease suffer from chronic debilitating pain and peripheral sensory neuropathy with minimal treatment options, but the cellular drivers of this pain are unknown. Here, we propose a novel mechanism by which altered signaling between Schwann cells and sensory neurons underlies the peripheral sensory nerve dysfunction we observe in a genetic rat model of Fabry disease. Using in vivo and in vitro electrophysiological recordings, we demonstrate that Fabry rat sensory neurons exhibit pronounced hyperexcitability. Schwann cells likely contribute to this finding as application of mediators released from cultured Fabry Schwann cells induces spontaneous activity and hyperexcitability in naïve sensory neurons. We examined putative algogenic mediators using proteomic analysis and found that Fabry Schwann cells release elevated levels of the protein p11 (S100-A10) which induces sensory neuron hyperexcitability. Removal of p11 from Fabry Schwann cell media causes hyperpolarization of neuronal resting membrane potential, indicating that p11 contributes to the excessive neuronal excitability caused by Fabry Schwann cells. These findings demonstrate that rats with Fabry disease exhibit sensory neuron hyperexcitability caused in part by Schwann cell release of the protein p11.
Author List
Waltz TB, Chao D, Prodoehl EK, Ehlers VL, Dharanikota BS, Dahms NM, Isaeva E, Hogan QH, Pan B, Stucky CLAuthors
Nancy M. Dahms PhD Professor in the Biochemistry department at Medical College of WisconsinQuinn H. Hogan MD Professor in the Anesthesiology department at Medical College of Wisconsin
Olena Isaeva PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin
Cheryl L. Stucky PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin
