UTHealth Houston - Graduate School of Biomedical Sciences

Roles of Satellite Glial Cells Driving Nociceptor Hyperexcitability after Spinal Cord Injury

Chrystine M. Gallegos, MS (Advisor: Carmen Dessauer, PhD)

          Satellite glial cells (SGCs) enwrap dorsal root ganglion (DRG) neurons and are increasingly recognized as key contributors to chronic pain. In neuropathic pain states, SGCs exhibit altered transcriptional profiles and increased expression of glial fibrillary acidic protein (GFAP), one possible indicator of SGC 'activation'. However, the potential circulating factors that drive SGC alterations and their regulatory influence on DRG neuron excitability are largely unknown. To address these gaps, I employed a culture of isolated neonatal SGCs that mirrors the signaling pathways and transcriptional landscape of SGCs within DRGs. Using this model, I screened circulating factors known to be elevated in rodent pain models and in patient chronic pain conditions for their stimulation of multiple signaling pathways in SGCs. One of these factors, transforming growth factor beta (TGFβ), induced GFAP expression and altered neonatal SGC gene expression, with TGFβ-induced differentially expressed genes (DEGs) overlapping with previously reported SGC DEGs in rodent models of neuropathic pain. TGFβ stimulation of isolated neonatal or adult SGCs, but not TGFβ or SGCs alone, promoted DRG neuron hyperexcitability and enhanced depolarizing spontaneous fluctuations—probable drivers of chronic pain. Furthermore, adult SGCs isolated from rats one month after spinal cord injury (SCI) maintained a cellular 'memory' of SCI that induced hyperexcitability of neurons from uninjured rats. Importantly, TGFβ treatment of human DRG cultures containing numerous SGCs also promoted neuronal hyperexcitability. As isolated SGCs were not in direct physical contact with neurons in my experiments but still managed to increase excitability, we hypothesized that SGCs are secreting neuroactive factors that alter neurons to promote hyperexcitability. Therefore, I analyzed proteins secreted by unaltered or TGFβ-altered SGCs using mass spectrometry of conditioned media, and show that upon stimulation by TGFβ, SGCs have significant changes to their secretome. Thus, factor-driven or SCI-driven alterations of SGCs results in fundamental changes to SGCs and their communication with neurons and ultimately increase DRG neuronal excitability, indicating the therapeutic potential of targeting SGCs for treatment of chronic pain.

Advisory Committee:

• Carmen Dessauer, PhD, Chair
• Michael Beierlein, PhD
• Shane Cunha, PhD
• Fabricio Do Monte, DVM, PhD
• Juan Herrera, PhD
• Edgar Walters, PhD

Join via Zoom (Please contact Ms. Gallegos for the details of her Zoom meeting info.)