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TNFa/TNFR2 signaling is required for glial ensheathment at the dorsal root entry zone.

ABSTRACT: Somatosensory information from the periphery is routed to the spinal cord through centrally-projecting sensory axons that cross into the central nervous system (CNS) via the dorsal root entry zone (DREZ). The glial cells that ensheath these axons ensure rapid propagation of this information. Despite the importance of this glial-axon arrangement, how this afferent nerve is assembled during development is unknown. Using in vivo, time-lapse imaging we show that as centrally-projecting pioneer axons from dorsal root ganglia (DRG) enter the spinal cord, they initiate expression of the cytokine TNFalpha. This induction coincides with ensheathment of these axons by associated glia via a TNF receptor 2 (TNFR2)-mediated process. This work identifies a signaling cascade that mediates peripheral glial-axon interactions and it functions to ensure that DRG afferent projections are ensheathed after pioneer axons complete their navigation, which promotes efficient somatosensory neural function.

SUBMITTER: Smith CJ

PROVIDER: S-EPMC5397050 | biostudies-other | 2017 Apr

REPOSITORIES: biostudies-other

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TNFa/TNFR2 signaling is required for glial ensheathment at the dorsal root entry zone.

Smith Cody J CJ Wheeler Michael A MA Marjoram Lindsay L Bagnat Michel M Deppmann Christopher D CD Kucenas Sarah S

PLoS genetics 20170405 4

Somatosensory information from the periphery is routed to the spinal cord through centrally-projecting sensory axons that cross into the central nervous system (CNS) via the dorsal root entry zone (DREZ). The glial cells that ensheath these axons ensure rapid propagation of this information. Despite the importance of this glial-axon arrangement, how this afferent nerve is assembled during development is unknown. Using in vivo, time-lapse imaging we show that as centrally-projecting pioneer axons ...[more]

PMID: 28379965

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Project description:Background: Postherpetic occipital neuralgia (PHON) is a neuropathic pain condition that usually presents as paroxysmal pain that is stabbing in nature.[5,7] It involves the occiput and posterior scalp in the distribution of the greater and/or lesser occipital nerves. It usually develops after an episode of shingles.[5,7] Treatment usually first consists of medical therapy and then progresses to invasive treatment (e.g., peripheral nerve stimulation, spinal cord epidural stimulation, C2-C3 ganglionectomy, or dorsal root entry zone [DREZ] rhizotomy).[1-4,6] Here, we present a case of persistent PHON that was treated with C1-C3 DREZ. Case Description: A 37-year-old female had a history of several episodes of shingles involving the left neck and occiput; they resolved after treatment with valacyclovir. Subsequently, however, she developed severe lancinating pain of the neck and the occiput and was diagnosed with PHON. Initially, she was treated with oxcarbazepine but was stopped due to cognitive side effects. She then had a cervical spinal cord stimulator implanted which produced relief for several years; it was later removed due to breakage of the electrodes. She then underwent a left- sided C1-C2 hemilaminectomy with a C1-C3 DREZ procedure.[1] Postoperatively, she had immediate resolution of her pain, but developed a new left hemiparesis (4+/5), accompanied by imbalance, decreased sensation to light touch, and loss of proprioception. On 6 weeks follow up, the pain was still relieved, and she exhibited significant improvement in her left-sided hemiparesis and hemisensory deficit to which returned to baseline. Similar outcome was maintained at four months follow up. Conclusion: Although high cervical DREZ lesions may effectively treat post herpetic/occipital neuralgia that fails other measures, there may be associated major neurological morbidity that makes this procedure acceptable as a salvage option, and after clearly explaining the risks to the patient.

Dataset Information

TNFa/TNFR2 signaling is required for glial ensheathment at the dorsal root entry zone.

Publications

TNFa/TNFR2 signaling is required for glial ensheathment at the dorsal root entry zone.

Similar Datasets

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