Faculty Collaboration Database

Fabry disease Schwann cells release p11 to induce sensory neuron hyperactivity. JCI Insight 2024 Mar 07;9(8)

Date

04/22/2024

Pubmed ID

38646936

Pubmed Central ID

PMC11141882

DOI

10.1172/jci.insight.172869

Scopus ID

2-s2.0-85191335156 (requires institutional sign-in at Scopus site)   3 Citations

Abstract

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 mechanism we believe to be novel in which altered signaling between Schwann cells and sensory neurons underlies the peripheral sensory nerve dysfunction we observed in a genetic rat model of Fabry disease. Using in vivo and in vitro electrophysiological recordings, we demonstrated that Fabry rat sensory neurons exhibited pronounced hyperexcitability. Schwann cells probably contributed to this finding because application of mediators released from cultured Fabry Schwann cells induced spontaneous activity and hyperexcitability in naive sensory neurons. We examined putative algogenic mediators using proteomic analysis and found that Fabry Schwann cells released elevated levels of the protein p11 (S100A10), which induced sensory neuron hyperexcitability. Removal of p11 from Fabry Schwann cell media caused hyperpolarization of neuronal resting membrane potentials, indicating that p11 may contribute to the excessive neuronal excitability caused by Fabry Schwann cells. These findings demonstrate that sensory neurons from rats with Fabry disease exhibit hyperactivity caused in part by Schwann cell release of the protein p11.

Author List

Waltz TB, Chao D, Prodoehl EK, Enders JD, Ehlers VL, Dharanikota BS, Dahms NM, Isaeva E, Hogan QH, Pan B, Stucky CL

Authors

Nancy M. Dahms PhD Professor in the Biochemistry department at Medical College of Wisconsin
Jonathan D. Enders Postdoctoral Researcher 2 in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin
Quinn 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

MESH terms used to index this publication - Major topics in bold

Animals
Cells, Cultured
Disease Models, Animal
Fabry Disease
Female
Male
Proteomics
Rats
Rats, Sprague-Dawley
Schwann Cells
Sensory Receptor Cells