A Novel Role for Lymphotactin (XCL1) Signaling in the Nervous System: XCL1 Acts via its Receptor XCR1 to Increase Trigeminal Neuronal Excitability
| Autor: | Emma V. Bird, Veselin I. Andreev, Anne King, Claire R. Christmas, Fiona M. Boissonade, Ilona Obara, Tommaso Iannitti |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Nervous system trigeminal nucleus Gene Expression Trigeminal Nuclei p38 Mitogen-Activated Protein Kinases CGRP calcitonin gene-related peptide Rats Sprague-Dawley Tissue Culture Techniques PCR polymerase chain reaction 0302 clinical medicine ERK extracellular signal-regulated kinase NDS normal donkey serum Vc trigeminal subnucleus caudalis Cy3 indocarbocyanine p38 p38 MAPK lymphotactin VGlut1 vesicular glutamate transporter 1 Extracellular Signal-Regulated MAP Kinases Neurons IB4 isolectin B4 Chemistry General Neuroscience orofacial pain 3. Good health Cell biology aCSF artificial cerebrospinal fluid medicine.anatomical_structure pp38 phosphorylated p38 Female Receptors Chemokine pERK phosphorylated ERK medicine.symptom Iba1 ionized calcium-binding adapter molecule 1 Proto-Oncogene Proteins c-fos vMIP-II viral CC chemokine macrophage inhibitory protein-II CCI chronic constriction injury PBS phosphate-buffered saline Schwann cell Calcitonin gene-related peptide Article OLIG2 03 medical and health sciences Facial Pain medicine Animals Trigeminal Nerve PBST PBS containing Triton-X TTX tetrodotoxin XCR1 lymphotactin receptor Rats Wistar neuronal excitability Trigeminal nerve chemokine GFAP glial fibrillary acidic protein Nerve injury Oligodendrocyte XCL1 lymphotactin Chemokines C 030104 developmental biology RT–PCR reverse transcriptase–PCR Neuralgia Trigeminal Nerve Injuries nerve injury PFA paraformaldehyde VGlut2 vesicular glutamate transporter 2 MAPK mitogen-activated protein kinase 030217 neurology & neurosurgery XCL1 |
| Zdroj: | Neuroscience |
| ISSN: | 0306-4522 |
| DOI: | 10.1016/j.neuroscience.2018.03.030 |
| Popis: | Highlights • We identified XCR1 in the peripheral and central nervous systems and demonstrated its upregulation following nerve injury. • In injured nerve, XCR1 is present in nerve fibers, CD45-positive leucocytes and Schwann cells. • In Vc, XCR1 labeling is consistent with expression in terminals of Aδ- and C-fiber afferents and excitatory interneurons. • XCL1 increases neuronal excitability and activates intracellular signaling in Vc, a pain-processing region of the CNS. • These data provide the first evidence that the XCL1-XCR1 axis may play a role in trigeminal pain pathways. Chemokines are known to have a role in the nervous system, influencing a range of processes including the development of chronic pain. To date there are very few studies describing the functions of the chemokine lymphotactin (XCL1) or its receptor (XCR1) in the nervous system. We investigated the role of the XCL1-XCR1 axis in nociceptive processing, using a combination of immunohistochemical, pharmacological and electrophysiological techniques. Expression of XCR1 in the rat mental nerve was elevated 3 days following chronic constriction injury (CCI), compared with 11 days post-CCI and sham controls. XCR1 co-existed with neuronal marker PGP9.5, leukocyte common antigen CD45 and Schwann cell marker S-100. In the trigeminal root and white matter of the brainstem, XCR1-positive cells co-expressed the oligodendrocyte marker Olig2. In trigeminal subnucleus caudalis (Vc), XCR1 immunoreactivity was present in the outer laminae and was colocalized with vesicular glutamate transporter 2 (VGlut2), but not calcitonin gene-related peptide (CGRP) or isolectin B4 (IB4). Incubation of brainstem slices with XCL1 induced activation of c-Fos, ERK and p38 in the superficial layers of Vc, and enhanced levels of intrinsic excitability. These effects were blocked by the XCR1 antagonist viral CC chemokine macrophage inhibitory protein-II (vMIP-II). This study has identified for the first time a role for XCL1-XCR1 in nociceptive processing, demonstrating upregulation of XCR1 at nerve injury sites and identifying XCL1 as a modulator of central excitability and signaling via XCR1 in Vc, a key area for modulation of orofacial pain, thus indicating XCR1 as a potential target for novel analgesics. |
| Databáze: | OpenAIRE |
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