Functional crosstalk in culture between macrophages and trigeminal sensory neurons of a mouse genetic model of migraine
Autor: | Elsa Fabbretti, Asha Nair, Arn M. J. M. van den Maagdenberg, Andrea Nistri, Alessia Franceschini, Tanja Bele |
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Rok vydání: | 2012 |
Předmět: |
Patch-Clamp Techniques
Calcium Channels L-Type Sensory Receptor Cells P2X3 receptor Purinergic receptor Pain Neuroinflammation ATP Sensitization Mice Transgenic Sensory system Cell Communication Biology lcsh:RC321-571 Membrane Potentials Mice Cellular and Molecular Neuroscience Trigeminal ganglion Adenosine Triphosphate Phagocytosis Tubulin Genetic model medicine Animals lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Cells Cultured Macrophages General Neuroscience lcsh:QP351-495 Calcium-Binding Proteins Microfilament Proteins Coculture Techniques Ganglion Mice Inbred C57BL Crosstalk (biology) lcsh:Neurophysiology and neuropsychology medicine.anatomical_structure Animals Newborn Trigeminal Ganglion Mutation Settore BIO/14 - Farmacologia Neuroscience Receptors Purinergic P2X3 Research Article |
Zdroj: | BMC Neuroscience BMC Neuroscience, 13 BMC Neuroscience, Vol 13, Iss 1, p 143 (2012) |
ISSN: | 1471-2202 |
DOI: | 10.1186/1471-2202-13-143 |
Popis: | Background Enhanced activity of trigeminal ganglion neurons is thought to underlie neuronal sensitization facilitating the onset of chronic pain attacks, including migraine. Recurrent headache attacks might establish a chronic neuroinflammatory ganglion profile contributing to the hypersensitive phenotype. Since it is difficult to study this process in vivo, we investigated functional crosstalk between macrophages and sensory neurons in primary cultures from trigeminal sensory ganglia of wild-type (WT) or knock-in (KI) mice expressing the Cacna1a gene mutation (R192Q) found in familial hemiplegic migraine-type 1. After studying the number and morphology of resident macrophages in culture, the consequences of adding host macrophages on macrophage phagocytosis and membrane currents mediated by pain-transducing P2X3 receptors on sensory neurons were examined. Results KI ganglion cultures constitutively contained a larger number of active macrophages, although no difference in P2X3 receptor expression was found. Co-culturing WT or KI ganglia with host macrophages (active as much as resident cells) strongly stimulated single cell phagocytosis. The same protocol had no effect on P2X3 receptor expression in WT or KI co-cultures, but it largely enhanced WT neuron currents that grew to the high amplitude constitutively seen for KI neurons. No further potentiation of KI neuronal currents was observed. Conclusions Trigeminal ganglion cultures from a genetic mouse model of migraine showed basal macrophage activation together with enhanced neuronal currents mediated by P2X3 receptors. This phenotype could be replicated in WT cultures by adding host macrophages, indicating an important functional crosstalk between macrophages and sensory neurons. |
Databáze: | OpenAIRE |
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