title: Interferon-gamma receptors are expressed at synapses in the rat superficial dorsal horn and lateral spinal nucleus.
abstract: Interferon-gamma can facilitate the spinal nociceptive flexor reflex and may elicit neuropathic pain-related behavior in rats and mice. Immunoreactivity for the interferon-gamma receptor (IFN-gamma R) occurs in the superficial layers of the dorsal horn and the lateral spinal nucleus in the rat and mouse spinal cord, as well as in subsets of neurons in the dorsal root ganglia. The aim of the present study was to examine the cellular localization and origin of the IFN-gamma R in the spinal cord. As viewed by confocal microscopy, the immunopositivity for the IFN-gamma R was co-localized with that of the presynaptic marker synaptophysin and with neuronal nitric oxide synthase in the lateral spinal nucleus, whereas only a minor overlap with these molecules was observed in laminae I and II of the dorsal horn. There was no co-localization of the IFN-gamma R with markers for astrocytes and microglial cells. Ultrastructurally, the IFN-gamma R was found predominantly in axon terminals in the lateral spinal nucleus, but at postsynaptic sites in dendrites in laminae I and II. The IFN-gamma R expressed in neurons in dorsal root ganglia was transported in axons both centrally and peripherally. Hemisection of the spinal cord caused no reduction in immunolabelling of the IFN-gamma R in the dorsal horn or the lateral spinal nucleus. Since rhizotomy does not affect the immunolabelling in the lateral spinal nucleus, our observation indicates that the presynaptic receptors in this nucleus are derived from intrinsic neurons. The localization of the IFN-gamma R in the spinal cord differed from that of the AMPA glutamate receptor subunits 2 and 3 and the substance P receptor (NK1). Our results, showing localization of IFN-gamma R to pre- and postsynaptic sites in the dorsal horn and lateral spinal nucleus indicate that IFN-gamma can modulate nociception at the spinal cord level.
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Vikman
authors.forename: B
authors.initials: B
authors.lastname: Robertson
authors.forename: G
authors.initials: G
authors.lastname: Grant
authors.forename: A
authors.initials: A
authors.lastname: Liljeborg
authors.forename: K
authors.initials: K
authors.lastname: Kristensson
mesh_terms: D000818:Animals; D015415:Biomarkers; D005260:Female; D005455:Fluorescent Antibody Technique; D008026:Ligation; D008297:Male; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D009457:Neuroglia / Q000737:chemistry; D019001:Nitric Oxide Synthase / Q000032:analysis; D052248:Nitric Oxide Synthase Type I; D009619:Nociceptors / Q000502:physiology; D020671:Posterior Horn Cells / Q000737:chemistry* / Q000201:enzymology / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000032:analysis; D017471:Receptors, Interferon / Q000032:analysis* / Q000096:biosynthesis; D018040:Receptors, Neurokinin-1 / Q000032:analysis; D012584:Sciatic Nerve / Q000601:surgery; D013116:Spinal Cord / Q000601:surgery; D013126:Spinal Nerve Roots / Q000601:surgery; D013569:Synapses / Q000737:chemistry* / Q000201:enzymology / Q000648:ultrastructure; D016708:Synaptophysin / Q000032:analysis; D000096743:Interferon gamma Receptor
chemical_list: D015415:Biomarkers; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D018091:Receptors, AMPA; D017471:Receptors, Interferon; D018040:Receptors, Neurokinin-1; D016708:Synaptophysin; D000096743:Interferon gamma Receptor; C496322:Nos1 protein, rat