Cisplatin-induced activation and functional modulation of satellite glial cells lead to cytokine-mediated modulation of sensory neuron excitability

2021 ◽  
Vol 341 ◽  
pp. 113695
Author(s):  
Markus Leo ◽  
Linda-Isabell Schmitt ◽  
Andrea Kutritz ◽  
Christoph Kleinschnitz ◽  
Tim Hagenacker
2020 ◽  
Vol 105 ◽  
pp. 103499
Author(s):  
Linda-Isabell Schmitt ◽  
Markus Leo ◽  
Andrea Kutritz ◽  
Christoph Kleinschnitz ◽  
Tim Hagenacker

Author(s):  
Mauricio A. Retamal ◽  
Manuel A. Riquelme ◽  
Jimmy Stehberg ◽  
Julio Alcayaga

2022 ◽  
Vol 14 ◽  
Author(s):  
Oshri Avraham ◽  
Pan-Yue Deng ◽  
Dario Maschi ◽  
Vitaly A. Klyachko ◽  
Valeria Cavalli

Among most prevalent deficits in individuals with Fragile X syndrome (FXS) is hypersensitivity to sensory stimuli and somatosensory alterations. Whether dysfunction in peripheral sensory system contributes to these deficits remains poorly understood. Satellite glial cells (SGCs), which envelop sensory neuron soma, play critical roles in regulating neuronal function and excitability. The potential contributions of SGCs to sensory deficits in FXS remain unexplored. Here we found major structural defects in sensory neuron-SGC association in the dorsal root ganglia (DRG), manifested by aberrant covering of the neuron and gaps between SGCs and the neuron along their contact surface. Single-cell RNAseq analyses demonstrated transcriptional changes in both neurons and SGCs, indicative of defects in neuronal maturation and altered SGC vesicular secretion. We validated these changes using fluorescence microscopy, qPCR, and high-resolution transmission electron microscopy (TEM) in combination with computational analyses using deep learning networks. These results revealed a disrupted neuron-glia association at the structural and functional levels. Given the well-established role for SGCs in regulating sensory neuron function, altered neuron-glia association may contribute to sensory deficits in FXS.


2019 ◽  
Vol 234 (11) ◽  
pp. 21199-21210 ◽  
Author(s):  
Jiu Lin ◽  
Fei Liu ◽  
Yan‐yan Zhang ◽  
Ning Song ◽  
Meng‐ke Liu ◽  
...  

2020 ◽  
Vol 16 ◽  
pp. 174480692092542 ◽  
Author(s):  
Seung Min Shin ◽  
Brandon Itson-Zoske ◽  
Yongsong Cai ◽  
Chensheng Qiu ◽  
Bin Pan ◽  
...  

Transient receptor potential ankyrin 1 (TRPA1) is well documented as an important molecule in pain hypersensitivity following inflammation and nerve injury and in many other cellular biological processes. Here, we show that TRPA1 is expressed not only by sensory neurons of the dorsal root ganglia (DRG) but also in their adjacent satellite glial cells (SGCs), as well as nonmyelinating Schwann cells. TRPA1 immunoreactivity is also detected in various cutaneous structures of sensory neuronal terminals, including small and large caliber cutaneous sensory fibers and endings. The SGC-expressed TRPA1 is functional. Like DRG neurons, dissociated SGCs exhibit a robust response to the TRPA1-selective agonist allyl isothiocyanate (AITC) by an increase of intracellular Ca2+ concentration ([Ca2+]i). These responses are abolished by the TRPA1 antagonist HC030031 and are absent in SGCs and neurons from global TRPA1 null mice. SGCs and neurons harvested from DRG proximal to painful tissue inflammation induced by plantar injection of complete Freund’s adjuvant show greater AITC-evoked elevation of [Ca2+]i and slower recovery compared to sham controls. Similar TRPA1 sensitization occurs in both SGCs and neurons during neuropathic pain induced by spared nerve injury. Together, these results show that functional TRPA1 is expressed by sensory ganglia SGCs, and TRPA1 function in SGCs is enhanced after both peripheral inflammation and nerve injury, and suggest that TRPA1 in SGCs may contribute to inflammatory and neuropathic pain.


2005 ◽  
Vol 289 (4) ◽  
pp. G670-G678 ◽  
Author(s):  
Tian-Ying Huang ◽  
Menachem Hanani

There is evidence that sensitization of neurons in dorsal root ganglia (DRG) may contribute to pain induced by intestinal injury. We hypothesized that obstruction-induced pain is related to changes in DRG neurons and satellite glial cells (SGCs). In this study, partial colonic obstruction was induced by ligation. The neurons projecting to the colon were traced by an injection of 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate into the colon wall. The electrophysiological properties of DRG neurons were determined using intracellular electrodes. Dye coupling was examined with an intracellular injection of Lucifer yellow (LY). Morphological changes in the colon and DRG were examined. Pain was assessed with von Frey hairs. Partial colonic obstruction caused the following changes. First, coupling between SGCs enveloping different neurons increased 18-fold when LY was injected into SGCs near neurons projecting to the colon. Second, neurons were not coupled to other neurons or SGCs. Third, the firing threshold of neurons projecting to the colon decreased by more than 40% ( P < 0.01), and the resting potential was more positive by 4–6 mV ( P < 0.05). Finally, the number of neurons displaying spontaneous spikes increased eightfold, and the number of neurons with subthreshold voltage oscillations increased over threefold. These changes are consistent with augmented neuronal excitability. The pain threshold to abdominal stimulation decreased by 70.2%. Inflammatory responses were found in the colon wall. We conclude that obstruction increased neuronal excitability, which is likely to be a major factor in the pain behavior observed. The augmented dye coupling between glial cells may contribute to the neuronal hyperexcitability.


Pain ◽  
2015 ◽  
Vol 156 (12) ◽  
pp. 2572-2584 ◽  
Author(s):  
Su Liu ◽  
Yue-Peng Liu ◽  
Zhi-Jiang Huang ◽  
Yan-Kai Zhang ◽  
Angela A. Song ◽  
...  

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