Secretagogin is Expressed in Sensory CGRP Neurons and in Spinal Cord of Mouse and Complements other Calcium-Binding Proteins, with a Note on Rat and Human

Abstract

BackgroundSecretagogin (Scgn), a member of the EF-hand calcium-binding protein (CaBP) superfamily, has recently been found in subsets of developing and adult neurons. Here, we have analyzed the expression of Scgn in dorsal root ganglia (DRGs) and trigeminal ganglia (TGs), and in spinal cord of mouse at the mRNA and protein levels, and in comparison to the well-known CaBPs, calbindin D-28k, parvalbumin and calretinin. Rat DRGs, TGs and spinal cord, as well as human DRGs and spinal cord were used to reveal phylogenetic variations.ResultsWe found Scgn mRNA expressed in mouse and human DRGs and in mouse ventral spinal cord. Our immunohistochemical data showed a complementary distribution of Scgn and the three CaBPs in mouse DRG neurons and spinal cord. Scgn was expressed in ~7% of all mouse DRG neuron profiles, mainly small ones and almost exclusively co-localized with calcitonin gene-related peptide (CGRP). This co-localization was also seen in human, but not in rat DRGs. Scgn could be detected in the mouse sciatic nerve and accumulated proximal to its constriction. In mouse spinal cord, Scgn-positive neuronal cell bodies and fibers were found in gray matter, especially in the dorsal horn, with particularly high concentrations of fibers in the superficial laminae, as well as in cell bodies in inner lamina II and in some other laminae. A dense Scgn-positive fiber network and some small cell bodies were also found in the superficial dorsal horn of humans. In the ventral horn, a small number of neurons were Scgn-positive in mouse but not rat, confirming mRNA distribution. Both in mouse and rat, a subset of TG neurons contained Scgn. Dorsal rhizotomy strongly reduced Scgn fiber staining in the dorsal horn. Peripheral axotomy did not clearly affect Scgn expression in DRGs, dorsal horn or ventral horn neurons in mouse.ConclusionsScgn is a CaBP expressed in a subpopulation of nociceptive DRG neurons and their processes in the dorsal horn of mouse, human and rat, the former two co-expressing CGRP, as well as in dorsal horn neurons in all three species. Functional implications of these findings include the cellular refinement of sensory information, in particular during the processing of pain.

Neuronal calcium-binding proteins 1/2 localize to dorsal root ganglia and excitatory spinal neurons and are regulated by nerve injury

“…In contrast to the high proportion of NECABs in small-and medium-sized neurons, the three principal CaBPs and Scgn exist in more circumscribed DRG neuron populations, and mainly in small-or large-sized ones (33). In DRGs, 1.1 ± 0.2% of the NECAB1 + NPs were PV + , 9.7 ± 0.8% were CB + , 0.2 ± 0.1% were CR + , and 3.0 ± 1.2% were Scgn + .…”

“…viii) NECAB2, in contrast to other CaBPs, is not confined to cell bodies/dendrites in the spinal cord but is also present in boutons/nerve endings, suggesting functions innate to synaptic neurotransmission. ix) NECAB1-LI and NECAB2-LIs were only detected in the cytoplasm, excluding the nucleus, whereas, for example, CB has a strong nuclear staining (17,33).…”

“…Fairly little is known about CaBPs in mouse DRG neurons, although Shi et al (33) showed that 7% are positive for Scgn.…”

“…In contrast, more data are available in the rat; however, in this species as well, the expression of classic EF-hand CaBPs (PV, CB, CR, and Scgn) is fairly restricted (18,33). Thus, ∼14% of DRG neurons are reported to be PV + and localized in largediameter neurons (43), with a similar proportion for CB in small-sized neurons (44).…”

Hypothalamic CNTF volume transmission shapes cortical noradrenergic excitability upon acute stress

“…Considering that NE inputs to the mPFC drive behavioral flexibility (Uematsu et al , 2017), we opted for behavioral paradigms that reveal sensory components of stress sensitivity without being reliant on enforcement or association (Tovote et al , 2015). Since secretagogin is expressed in sensory dorsal root ganglia (Shi et al , 2012a), we first verified that Scgn −/− mice had unchanged sensory thresholds in the von Frey filament test, as compared to wild‐type littermates ( P  =   0.19; Fig EV3C). Thereafter, we showed that Scgn −/− mice produce reduced escape responses when triggering their pinna reflex (Fig EV3C1) or exposing them to toe pinch ( P  <   0.05 vs. wild‐type littermates; Fig EV3C2).…”