Nociceptor-like rat dorsal root ganglion neurons express the angiotensin-II AT2 receptor throughout development. Issue 56 (February 2017)

• Record Type: Journal Article
• Authors: Benitez, Sergio; Seltzer, Alicia; Acosta, Cristian
• Is Part Of: International journal of developmental neuroscience. Issue 56(2017:Feb.)
• Page Start: 10
• Page End: 17
• Publication Date: 2017-02
• Subjects: DRG dorsal root ganglia -- GAPDH glyceraldehyde-3-phosphate dehydrogenase -- AT2R angiotensin-II type 2 receptor -- IB4 isolectin B4 -- Ret receptor for the glial-derived growth factor -- GDNF glial-derived neurotrophic factor -- trkA tropomyosin receptor kinase A -- Adr Adrenal cortex; Angiotensin-II -- Sensory neurons -- Pain -- Ret -- IB4 -- TrkA; Developmental neurobiology -- Periodicals; Neurology -- Periodicals; Neurologie du développement -- Périodiques; Developmental neurobiology; Periodicals; 612.8
• DOI: 10.1016/j.ijdevneu.2016.11.001
• Languages: English
• ISSNs: 0736-5748

Abstract

Highlights: Dorsal root ganglion neurons express AT2R at constant levels throughout development. AT2R co-expresses with trkA at E15 and with both trkA and Ret at E18. Small IB4-binding C-nociceptors express AT2R postnatally. AT2R expression pattern resembles that of typical phenotypic markers of nociceptors. Abstract: AT2 receptor (AT2R) plays a functional role in foetal development. Its expression declines in most tissues soon after birth but stays high in sensory areas of the adult nervous system. In the dorsal root ganglia (DRG) the expression pattern of AT2R during development and the identity of the subpopulation expressing it remain unknown. Using a combination of semi-quantitative PCR, western blotting and immunohistochemistry we examined the expression of AT2R at mRNA and protein levels in rat DRGs from embryonic day 15 (E15) until postnatal day 30 (PN30). We found that both AT2R mRNA and protein levels exhibited only minor (statistically non-significant) fluctuations from E15 to PN30. Detailed quantitative analysis of ABC/DAB AT2R staining showed a) that the receptor was present in most neurons at E15 and E18 and b) that postnatally it was predominantly expressed by small DRG neurons. Given that small neurons are putative C-nociceptors and the proposed role of AT2R in neuropathic pain, we next examined whether these AT2R-positive neurons co-localized with Ret and trkA embryonically and with IB4-binding postnatally. Most AT2R-positive neurons expressed trkA embryonically and bound IB4 postnatally. We found strong positive statistically highly significant correlations between AT2R cytoplasmic%intensities and trkA at E15/E18 and with Ret only at E18. Cytoplasmic AT2R also strongly and positively correlated with IB4-binding at PN3, 15 and 30. Our demonstration that a subpopulation of C-nociceptor-like neurons expresses AT2R during development supports a role for this receptor in neuropathic pain.