Aquaporin 4 expression on trigeminal satellite glial cells under normal and inflammatory conditions

2017 ◽  
Vol 16 (1) ◽  
pp. 183-184
Author(s):  
D. Riccio ◽  
G. Magni ◽  
S. Ceruti ◽  
L. Arendt-Nielsen ◽  
P. Gazerani
Keyword(s):  
Glial Cells ◽  
Trigeminal Ganglia ◽  
Sensory Ganglia ◽  
Satellite Glial Cells ◽  
Pain Model ◽  
Aqp4 Expression ◽  
Inflammatory Conditions ◽  
Trigeminal Neurons ◽  
Deficient Mice

AbstractAimsLimited information is currently available for the expression and role of Aquaporin 4 (AQP4) (AQ4) in the peripheral nervous system (PNS). It has been demonstrated that AQP4 is expressed in sensory ganglia. Immunohistochemistry has revealed that satellite glial cells (SGCs) surrounding the cell bodies of the primary afferent sensory neurons in these sensory ganglia exclusively express AQP4 at a considerably lower level than what is seen in astrocytes. The pathophysiological relevance of AQP4 in peripheral nociception; however, remains unclear. Hence, this study aimed at investigating AQP4 expression in trigeminal neurons and SGCs under normal and inflammatory conditions relevant to craniofacial pain conditions.MethodsRat trigeminal ganglia (TG) were isolated from adult male Sprague-Dawley rats subjected to a model of trigeminal inflammation evoked by unilateral complete Freund’s adjuvant (CFA) injection in temporomandibular joint. Immunohistochemistry was performed on TG sections of CFA-treated animals. NeuN and GS markers were used for identification of neurons and SGCs, respectively. AQP4 expression was investigated in both ipsilateral and contralateral TG sections. The study protocol was approved by the local ethics committee.ResultsCo-localization of NeuN-AQP4 and GS-AQP4 were identified in both ipsi and contralateral trigeminal ganglia of the CFA-treated rats. However, we did not detect any difference between the ipsi- and contralateral side in terms of alteration in AQP4 receptor expression.ConclusionsAQP4 was expressed both on trigeminal neurons and SGCs and CFA did not cause a remarkable change in AQP4 expression, when ipsilateral and contralateral TG of the test animals was compared. Previously, it has been shown that in a neuropathic pain model no difference is detectable between wild type and AQP4-deficient mice, for mechanical and thermal perception; however, in formalin pain model AQP4-deficient mice have higher thermal pain thresholds. Further investigation is required to clarify role of AQP4 in pain.

scholarly journals Hemokinin-1 Gene Expression Is Upregulated in Trigeminal Ganglia in an Inflammatory Orofacial Pain Model: Potential Role in Peripheral Sensitization

2020 ◽  
Vol 21 (8) ◽  
pp. 2938
Author(s):  
Timea Aczél ◽  
Angéla Kecskés ◽  
József Kun ◽  
Kálmán Szenthe ◽  
Ferenc Bánáti ◽  
...  
Keyword(s):  
Gene Expression ◽  
Glial Cells ◽  
Orofacial Pain ◽  
Model Potential ◽  
Trigeminal System ◽  
Trigeminal Ganglia ◽  
Peripheral Sensitization ◽  
Satellite Glial Cells ◽  
Pain Model ◽  
Nociceptive Neurons

A large percentage of primary sensory neurons in the trigeminal ganglia (TG) contain neuropeptides such as tachykinins or calcitonin gene-related peptide. Neuropeptides released from the central terminals of primary afferents sensitize the secondary nociceptive neurons in the trigeminal nucleus caudalis (TNC), but also activate glial cells contributing to neuroinflammation and consequent sensitization in chronic orofacial pain and migraine. In the present study, we investigated the newest member of the tachykinin family, hemokinin-1 (HK-1) encoded by the Tac4 gene in the trigeminal system. HK-1 had been shown to participate in inflammation and hyperalgesia in various models, but its role has not been investigated in orofacial pain or headache. In the complete Freund’s adjuvant (CFA)-induced inflammatory orofacial pain model, we showed that Tac4 expression increased in the TG in response to inflammation. Duration-dependent Tac4 upregulation was associated with the extent of the facial allodynia. Tac4 was detected in both TG neurons and satellite glial cells (SGC) by the ultrasensitive RNAscope in situ hybridization. We also compared gene expression changes of selected neuronal and glial sensitization and neuroinflammation markers between wild-type and Tac4-deficient (Tac4-/-) mice. Expression of the SGC/astrocyte marker in the TG and TNC was significantly lower in intact and saline/CFA-treated Tac4-/- mice. The procedural stress-related increase of the SGC/astrocyte marker was also strongly attenuated in Tac4-/- mice. Analysis of TG samples with a mouse neuroinflammation panel of 770 genes revealed that regulation of microglia and cytotoxic cell-related genes were significantly different in saline-treated Tac4-/- mice compared to their wild-types. It is concluded that HK-1 may participate in neuron-glia interactions both under physiological and inflammatory conditions and mediate pain in the trigeminal system.

Quiescent satellite glial cells of the adult trigeminal ganglion

Open Medicine ◽  
2014 ◽  
Vol 9 (3) ◽  
pp. 500-504 ◽  
Author(s):  
Mugurel Rusu ◽  
Valentina Mănoiu ◽  
Nicolae Mirancea ◽  
Gheorghe Nini
Keyword(s):  
Electron Microscopy ◽  
Glial Cells ◽  
Trigeminal Ganglion ◽  
Membrane Trafficking ◽  
Animal Species ◽  
Trigeminal Ganglia ◽  
Sensory Ganglia ◽  
Satellite Glial Cells ◽  
Transmission Electron ◽  
Immune Phenotypes

AbstractSensory ganglia comprise functional units built up by neurons and satellite glial cells (SGCs). In animal species there was proven the presence of neuronoglial progenitor cells in adult samples. Such neural crest-derived progenitors were found in immunohistochemistry (IHC). These findings were not previously documented in transmission electron microscopy (TEM). It was thus aimed to assess in TEM if cells of the human adult trigeminal ganglion indeed have ultrastructural features to qualify for a progenitor, or quiescent phenotype. Trigeminal ganglia were obtained from fifteen adult donor cadavers. In TEM, cells with heterochromatic nuclei, a pancytoplasmic content of free ribosomes, few perinuclear mitochondria, poor developed endoplasmic reticulum, lack of Golgi complexes and membrane trafficking specializations, were found included in the neuronal envelopes built-up by SGCs. The ultrastructural pattern was strongly suggestive for these cells being quiescent progenitors. However, further experiments should correlate the morphologic and immune phenotypes of such cells.

scholarly journals Bidirectional calcium signaling between satellite glial cells and neurons in cultured mouse trigeminal ganglia

2009 ◽  
Vol 6 (1) ◽  
pp. 43-51 ◽  
Author(s):  
Sylvia O. Suadicani ◽  
Pavel S. Cherkas ◽  
Jonathan Zuckerman ◽  
David N. Smith ◽  
David C. Spray ◽  
...  
Keyword(s):  
Calcium Signaling ◽  
Sensory Neurons ◽  
Glial Cells ◽  
Mechanical Stimulation ◽  
Calcium Concentration ◽  
Cytosolic Calcium ◽  
Trigeminal Ganglia ◽  
Sensory Ganglia ◽  
Satellite Glial Cells ◽  
First Time

Astrocytes communicate with neurons, endothelial and other glial cells through transmission of intercellular calcium signals. Satellite glial cells (SGCs) in sensory ganglia share several properties with astrocytes, but whether this type of communication occurs between SGCs and sensory neurons has not been explored. In the present work we used cultured neurons and SGCs from mouse trigeminal ganglia to address this question. Focal electrical or mechanical stimulation of single neurons in trigeminal ganglion cultures increased intracellular calcium concentration in these cells and triggered calcium elevations in adjacent glial cells. Similar to neurons, SGCs responded to mechanical stimulation with increase in cytosolic calcium that spread to the adjacent neuron and neighboring glial cells. Calcium signaling from SGCs to neurons and among SGCs was diminished in the presence of the broad-spectrum P2 receptor antagonist suramin (50 μM) or in the presence of the gap junction blocker carbenoxolone (100 μM), whereas signaling from neurons to SGCs was reduced by suramin, but not by carbenoxolone. Following induction of submandibular inflammation by Complete Freund's Adjuvant injection, the amplitude of signaling among SGCs and from SGCs to neuron was increased, whereas the amplitude from neuron to SGCs was reduced. These results indicate for the first time the presence of bidirectional calcium signaling between neurons and SGCs in sensory ganglia cultures, which is mediated by the activation of purinergic P2 receptors, and to some extent by gap junctions. Furthermore, the results indicate that not only sensory neurons, but also SGCs release ATP. This form of intercellular calcium signaling likely plays key roles in the modulation of neuronal activity within sensory ganglia in normal and pathological states.

Expression and contribution of satellite glial cells purinoceptors to pain transmission in sensory ganglia: an update

2010 ◽  
Vol 6 (1) ◽  
pp. 31-42 ◽  
Author(s):  
Giovanni Villa ◽  
Marta Fumagalli ◽  
Claudia Verderio ◽  
Maria P. Abbracchio ◽  
Stefania Ceruti
Keyword(s):  
Glial Cells ◽  
Pain Treatment ◽  
Purinergic Signaling ◽  
Original Data ◽  
P2y Receptors ◽  
Receptor Expression ◽  
Sensory Ganglia ◽  
Satellite Glial Cells ◽  
Pain Transmission

The role of adenosine-5′-triphosphate (ATP) and of the ligand-gated P2X3receptor in neuronal dorsal root ganglia (DRG) pain transmission is relatively well established. Much less is known about the purinergic system in trigeminal ganglia (TG), which are involved in certain types of untreatable neuropathic and inflammatory pain, as well as in migraine. Emerging data suggest that purinergic metabotropic P2Y receptors on both neurons and satellite glial cells (SGCs) may also participate in both physiological and pathological pain development. Here, we provide an updated literature review on the role of purinergic signaling in sensory ganglia, with special emphasis on P2Y receptors on SGCs. We also provide new original data showing a time-dependent downregulation of P2Y2and P2Y4receptor expression and function in purified SGCs cultures from TG, in comparison with primary mixed neuron–SGCs cultures. These data highlight the importance of the neuron–glia cross-talk in determining the SGCs phenotype. Finally, we show that, in mixed TG cultures, both adenine and guanosine induce intracellular calcium transients in neurons but not in SGCs, suggesting that also these purinergic-related molecules can participate in pain signaling. These findings may have relevant implications for the development of new therapeutic strategies for chronic pain treatment.

scholarly journals Satellite glial cells in sensory ganglia express functional transient receptor potential ankyrin 1 that is sensitized in neuropathic and inflammatory pain

2020 ◽  
Vol 16 ◽  
pp. 174480692092542 ◽  
Author(s):  
Seung Min Shin ◽  
Brandon Itson-Zoske ◽  
Yongsong Cai ◽  
Chensheng Qiu ◽  
Bin Pan ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Nerve Injury ◽  
Glial Cells ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Allyl Isothiocyanate ◽  
Sensory Ganglia ◽  
Satellite Glial Cells ◽  
Intracellular Ca ◽  
Transient Receptor

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.

scholarly journals N/OFQ modulates orofacial pain induced by tooth movement through CGRP-dependent pathways

2020 ◽  
Author(s):  
Xinyu Yan ◽  
Han Han ◽  
Shizhen Zhang ◽  
Yanzhu Lu ◽  
Linghuan Ren ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Tooth Movement ◽  
Orofacial Pain ◽  
Pain Modulation ◽  
Trigeminal Ganglia ◽  
Orphanin Fq ◽  
Pain Model ◽  
Calcitonin Gene ◽  
Agonist And Antagonist

Abstract Background: Nociceptin/orphanin FQ (N/OFQ) has been revealed to play bidirectional roles in orofacial pain modulation. Calcitonin gene-related peptide (CGRP) is a well-known pro-nociceptive molecule that participates in the modulation of orofacial pain. We aimed to determine the effects of N/OFQ on the modulation of orofacial pain and on the release of CGRP.Methods: Orofacial pain model was established by ligating springs between incisors and molars in rats for the simulation of tooth movement. The expression level of N/OFQ was determined and pain level scored in response to orofacial pain. Both agonist and antagonist of N/OFQ receptor were administered to examine their effects on pain and the expression of CGRP in trigeminal ganglia (TG). Moreover, gene therapy based on the overexpression of N/OFQ was delivered to validate the modulatory role of N/OFQ on pain and CGRP expression.Results: Tooth movement elicited orofacial pain and an elevation in N/OFQ expression. N/OFQ exacerbated orofacial pain and upregulated CGRP expression in TG, while UFP-101 alleviated pain and downregulated CGRP expression. N/OFQ-based gene therapy was successful in overexpressing N/OFQ in TG, which resulted in pain exacerbation and elevation of CGRP expression in TG.Conclusions: N/OFQ exacerbated orofacial pain possibly through upregulating CGRP.

scholarly journals N/OFQ modulates orofacial pain induced by tooth movement through CGRP-dependent pathways

2020 ◽  
Author(s):  
Xinyu Yan ◽  
Han Han ◽  
Shizhen Zhang ◽  
Yanzhu Lu ◽  
Linghuan Ren ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Tooth Movement ◽  
Orofacial Pain ◽  
Pain Modulation ◽  
Trigeminal Ganglia ◽  
Orphanin Fq ◽  
Pain Model ◽  
Calcitonin Gene ◽  
Agonist And Antagonist

Abstract Background: Nociceptin/orphanin FQ (N/OFQ) has been revealed to play bidirectional roles in orofacial pain modulation. Calcitonin gene-related peptide (CGRP) is a well-known pro-nociceptive molecule that participates in the modulation of orofacial pain. We aimed to determine the effects of N/OFQ on the modulation of orofacial pain and on the release of CGRP.Methods: Orofacial pain model was established by ligating springs between incisors and molars in rats for the simulation of tooth movement. The expression level of N/OFQ was determined and pain level scored in response to orofacial pain. Both agonist and antagonist of N/OFQ receptor were administered to examine their effects on pain and the expression of CGRP in trigeminal ganglia (TG). Moreover, gene therapy based on the overexpression of N/OFQ was delivered to validate the modulatory role of N/OFQ on pain and CGRP expression.Results: Tooth movement elicited orofacial pain and an elevation in N/OFQ expression. N/OFQ exacerbated orofacial pain and upregulated CGRP expression in TG, while UFP-101 alleviated pain and downregulated CGRP expression. N/OFQ-based gene therapy was successful in overexpressing N/OFQ in TG, which resulted in pain exacerbation and elevation of CGRP expression in TG.Conclusions: N/OFQ exacerbated orofacial pain possibly through upregulating CGRP.

Abstract 307: Role of Epsins in Regulating LPS-Induced Sepsis

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Satish Pasula ◽  
Megan L Brophy ◽  
Kandice L Tessneer ◽  
Scott Hahn ◽  
John McManus ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Tissue Injury ◽  
Lethal Dose ◽  
Surface Protein ◽  
Inflammatory Conditions ◽  
Fundamental Information ◽  
Subsequent Degradation ◽  
Surface Protein Expression ◽  
Deficient Mice

Background: Sepsis is caused by a deleterious host response to infection, which is primarily responsible for further injury of host tissue and cause of organ dysfunction. However, the underlying regulatory mechanisms are still not fully understood. Our goal is to define the novel role of epsins in regulating sepsis. Methods and Results: We engineered global (iDKO) and endothelial cell-specific (EC-iDKO) epsin deficient mice. When treated with lethal dose of LPS, epsin deficient mice were completely protected from LPS-induced septic death. These mice also exhibited decreased expression of tissue damage biomarkers and recruitment of neutrophils and macrophages to lungs compared to wild type (WT) suggesting that epsin deficiency mitigates sepsis induced tissue injury. Epsin deficiency further reduced expression of proinflammatory cytokines and adhesion molecules in the lungs suggesting that loss of epsin attenuates LPS-induced inflammatory responses. TAT complex production was also decreased in iDKO mice compared to WT indicating diminished coagulation and thrombin production. Knocking down of epsins in HUVECs resulted in reduced cell surface Tissue Factor (TF) expression. Loss of epsin in mice protected against loss of Thrombomodulin (TM), which is downregulated by sepsis. Mechanistically, loss of epsin inhibited LPS-induced TM internalization, while LPS treatment induced the ubiquitination of TM. Furthermore, co-IP of full length epsin 1 or epsin 1 without the UIM domain and TM demonstrated that UIM is required for the interaction between epsin 1 and TM. Collectively, we show that epsin-deficiency upregulates TM surface protein expression by preventing its internalization and subsequent degradation and inhibits heightened TF expression and activation under chronic inflammatory conditions such as that induced by LPS exposure. Conclusions: Our findings demonstrate that epsins play a key role in regulating coagulation and provide fundamental information on the modulation of the ratio of TM/TF in various thrombotic diseases including sepsis. Furthermore, we demonstrate loss of epsin protects mice against LPS-induced sepsis, suggesting a crucial role for epsins in promoting the development of LPS-induced sepsis.

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