Activity-dependent secretion of neuronal activity regulated pentraxin from vasopressin neurons into the systemic circulation

Abstract

Neuronal activity regulated pentraxin (Narp) is a secreted, synaptic protein that has been implicated in modulating synaptic transmission. However, it is unclear how Narp secretion is regulated. Since we noted prominent Narp immunostaining in vasopressin neurons of the hypothalamus and in the posterior pituitary, we assessed whether it, like vasopressin, is released into the systemic circulation in an activity-dependent fashion. Consistent with this hypothesis, electron microscopic studies of the posterior pituitary demonstrated that Narp is located in secretory vesicles containing vasopressin. Using affinity chromatography, we detected Narp in plasma and found that these levels are markedly decreased by hypophysectomy. In addition, we confirmed that injection of a viral Narp construct into the hypothalamus restores plasma Narp levels in Narp knockout mice. In checking for activity-dependent secretion of Narp from the posterior pituitary, we found that several stimuli known to trigger vasopressin release, i.e. hypovolemia, dehydration and endotoxin, elevate plasma Narp levels. Taken together, these findings provide compelling evidence that Narp is secreted from vasopressin neurons in an activity-dependent fashion.

Selective expression of Narp in primary nociceptive neurons: Role in microglia/macrophage activation following nerve injury

“…This pattern of Narp localization in axons and terminals is also consistent with previous studies that have demonstrated that Narp, which is a secreted protein, is trafficked down axons to terminals in other pathways, e.g. mossy fibers of dentate granule cells (Reti et al, 2002b) and to vasopressin terminals in the posterior pituitary (Reti et al, 2008a). Moreover, electron microscopy studies have also shown that vasopressin (Reti et al, 2008a) and orexin (I.M.…”

“…For example, in the hippocampus, Narp is selectively expressed in dentate granule cells (Reti et al, 2002b). In the hypothalamus, Narp is only expressed in a small population of neurons, including orexin and vasopressin neurons (Reti et al, 2002c and 2008a). We also observed Narp terminal staining in the dorsal horn of the spinal cord which was markedly reduced by dorsal rhizotomy, suggesting Narp is trafficked to the dorsal horn from DRG neurons.…”

“…Immunogold studies of Narp localization were performed as described previously (Reti et al, 2008a). Briefly, mice were perfused with 4% paraformaldehyde with 0.5% glutaraldehyde and sections of tissue were frozen in liquid propane in a Leica CPC cryopreparation chamber and then freeze-substituted into Lowicryl HM-20 in a Leica AFS.…”

“…For example, Narp is localized selectively to dentate granule cells in the hippocampus (Reti et al, 2002b), to the anterdorsal nucleus in the thalamus (Reti et al, 2002a), and to a small subset of neurons in the hypothalamus, including orexin and vasopressin neurons (Reti et al, 2002c; Reti et al, 2008a). As part of a survey of Narp expression in the nervous system, we identified Narp expression in dorsal root ganglia (DRG), where it appeared to be expressed predominantly in small diameter neurons, characteristic of primary nociceptive neurons.…”

Excitation-Transcription Coupling via Calcium/Calmodulin-dependent Protein Kinase/ERK1/2 Signaling Mediates the Coordinate Induction of VGLUT2 and Narp Triggered by a Prolonged Increase in Glutamatergic Synaptic Activity

“…Narp is a recognized intermediate-early gene product induced by hyperactivity in vivo (24,55,99). Here, we show that Narp mRNA expression is dramatically induced together with VGLUT2 after a prolonged increase in endogenous glutamatergic synaptic activation of neocortical neuronal networks in vitro.…”