Connexin43 Hemichannels in Satellite Glial Cells, Can They Influence Sensory Neuron Activity?

Retamal, Mauricio A.; Riquelme, Manuel A.; Stehberg, Jimmy; Alcayaga, Julio

doi:10.3389/fnmol.2017.00374

Cited by 35 publications

(17 citation statements)

References 102 publications

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“…We avoided modulating Cx43 in these cell types by using the Sox10 promoter to specifically target peripheral glia. Changes to Cx43 expression in satellite glial cells could contribute to the analgesic effects we observed here (Britsch et al, 2001;Retamal et al, 2017), but this scenario is unlikely since Sox10 CreERT2 ;Cx43 f/f animals exhibit VMRs comparable to control littermates at baseline conditions and during acute inflammation.…”

Section: Cell Reportsmentioning

confidence: 90%

Enteric Glia Modulate Macrophage Phenotype and Visceral Sensitivity following Inflammation

et al. 2020

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SUMMARY Mechanisms resulting in abdominal pain include altered neuro-immune interactions in the gastrointestinal tract, but the signaling processes that link immune activation with visceral hypersensitivity are unresolved. We hypothesized that enteric glia link the neural and immune systems of the gut and that communication between enteric glia and immune cells modulates the development of visceral hypersensitivity. To this end, we manipulated a major mechanism of glial intercellular communication that requires connexin-43 and assessed the effects on acute and chronic inflammation, visceral hypersensitivity, and immune responses. Deleting connexin-43 in glia protected against the development of visceral hypersensitivity following chronic colitis. Mechanistically, the protective effects of glial manipulation were mediated by disrupting the glial-mediated activation of macrophages through the macrophage colony-stimulating factor. Collectively, our data identified enteric glia as a critical link between gastrointestinal neural and immune systems that could be harnessed by therapies to ameliorate abdominal pain.

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Section: Cell Reportsmentioning

confidence: 90%

Enteric Glia Modulate Macrophage Phenotype and Visceral Sensitivity following Inflammation

et al. 2020

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“…glutamate aspartate transporter: GLAST [13]], and channels [e.g. inwardly rectifying K + channel 4.1 (Kir 4.1) [14]; connexin 43 (Cx43)-based gap junctions and hemichannels [15]]. As astrocytes and many other cell types, SGCs use Ca 2+ as a signaling molecule [16].…”

Section: Introductionmentioning

confidence: 99%

Characterization of transgenic mouse lines for selectively targeting satellite glial cells and macrophages in dorsal root ganglia

Rabah¹,

Rubino²,

Moukarzel³

et al. 2020

PLoS ONE

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The importance of glial cells in the modulation of neuronal processes is now generally accepted. In particular, enormous progress in our understanding of astrocytes and microglia physiology in the central nervous system (CNS) has been made in recent years, due to the development of genetic and molecular toolkits. However, the roles of satellite glial cells (SGCs) and macrophages-the peripheral counterparts of astrocytes and microglia-remain poorly studied despite their involvement in debilitating conditions, such as pain. Here, we characterized in dorsal root ganglia (DRGs), different genetically-modified mouse lines previously used for studying astrocytes and microglia, with the goal to implement them for investigating DRG SGC and macrophage functions. Although SGCs and astrocytes share some molecular properties, most tested transgenic lines were found to not be suitable for studying selectively a large number of SGCs within DRGs. Nevertheless, we identified and validated two mouse lines: (i) a CreERT2 recombinase-based mouse line allowing transgene expression almost exclusively in SGCs and in the vast majority of SGCs, and (ii) a GFP-expressing line allowing the selective visualization of macrophages. In conclusion, among the tools available for exploring astrocyte functions, a few can be used for studying selectively a great proportion of SGCs. Thus, efforts remain to be made to characterize other available mouse lines as well as to develop, rigorously characterize and validate new molecular tools to investigate the roles of DRG SGCs, but also macrophages, in health and disease.

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“…Recent evidence suggests that activity of the satellite glial cells connected with gap junctions and reduces the pain threshold in the trigeminal ganglion. Furthermore, inhibition of satellite glial cell activation causes a significant reduction in neuronal excitability and nocifensive reflexes [43,44]. Otherwise, the proximity of satellite glial cells and neuronal cell bodies favours interactions through paracrine signalling and contributes to the sensitization of afferent neurons.…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of Fucoxanthin on Ultraviolet B-Induced Corneal Denervation and Inflammatory Pain in a Rat Model

et al. 2019

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Fucoxanthin is a carotenoid with many pharmaceutical properties that is found in brown seaweed. However, the effects of fucoxanthin on corneal innervation and intense eye pain have not been extensively examined. To clarify the protective roles and underlying mechanisms of fucoxanthin on ocular lesions, we investigated the beneficial effects and mechanisms by which fucoxanthin ameliorates ultraviolet B (UVB)-induced corneal denervation and trigeminal pain. Treatment with fucoxanthin enhanced the expression of nuclear factor erythroid 2-related factor 2 in the cornea. Inhibition of typical denervation and epithelial exfoliation in the cornea were observed in rats treated with fucoxanthin following UVB-induced nerve disorders. Moreover, the active phosphorylated form of p38 MAP kinase (pp38) and the number of glial fibrillary acidic protein (GFAP)-positive neural cells were significantly reduced. Decreased expression of neuron-selective transient receptor potential vanilloid type 1 (TRPV1) in the trigeminal ganglia neurons was also demonstrated in rats treated with fucoxanthin after UVB-induced keratitis. Symptoms of inflammatory pain, including difficulty in opening the eyes and eye wipe behaviour, were also reduced in fucoxanthin-treated groups. Pre-treatment with fucoxanthin may protect the eyes from denervation and inhibit trigeminal pain in UVB-induced photokeratitis models.

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Connexin43 Hemichannels in Satellite Glial Cells, Can They Influence Sensory Neuron Activity?

Cited by 35 publications

References 102 publications

Enteric Glia Modulate Macrophage Phenotype and Visceral Sensitivity following Inflammation

Enteric Glia Modulate Macrophage Phenotype and Visceral Sensitivity following Inflammation

Characterization of transgenic mouse lines for selectively targeting satellite glial cells and macrophages in dorsal root ganglia

Protective Effects of Fucoxanthin on Ultraviolet B-Induced Corneal Denervation and Inflammatory Pain in a Rat Model

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