Expression of prokineticins and their receptors in the adult mouse brain

Abstract

Prokineticins are a pair of regulatory peptides that have been shown to play important roles in gastrointestinal motility, angiogenesis, circadian rhythms, and, recently, olfactory bulb neurogenesis. Prokineticins exert their functions via activation of two closely related G-protein-coupled receptors. Here we report a comprehensive mRNA distribution for both prokineticins (PK1 and PK2) and their receptors (PKR1 and PKR2) in the adult mouse brain with the use of in situ hybridization. PK2 mRNA is expressed in discrete regions of the brain, including suprachiasmatic nucleus, islands of Calleja and medial preoptic area, olfactory bulb, nucleus accumbens shell, hypothalamic arcuate nucleus, and amygdala. PK1 mRNA is expressed exclusively in the brainstem, with high abundance in the nucleus tractus solitarius. PKR2 mRNA is detected throughout the brain, with prominent expression in olfactory regions, cortex, thalamus and hypothalamus, septum and hippocampus, habenula, amygdala, nucleus tractus solitarius, and circumventricular organs such as subfornical organ, median eminence, and area postrema. PKR2 mRNA is also detected in mammillary nuclei, periaqueductal gray, and dorsal raphe. In contrast, PKR1 mRNA is found in fewer brain regions, with moderate expression in the olfactory regions, dentate gyrus, zona incerta, and dorsal motor vagal nucleus. Both PKR1 and PKR2 are also detected in olfactory ventricle and subventricular zone of the lateral ventricle, both of which are rich sources of neuronal precursors. These extensive expression patterns suggest that prokineticins may have a broad array of functions in the central nervous system, including circadian rhythm, neurogenesis, ingestive behavior, reproduction, and autonomic function.

The Mammalian Circadian Timing System: Organization and Coordination of Central and Peripheral Clocks

“…PK2 receptor mRNA expression is observed in many brain areas known to receive SCN efferents including the DMH, the LS, and the PVN (Figure 1b). Exogenous application of PK2 suppresses locomotor activity in rats during the night but increases it during the day, indicating that PK2 transmits circadian activity of the SCN (74,79). However, mice lacking PK2 or the PK2 receptor display dampened rhythms in activity and thermoregulation, suggesting that factors other than PK2 can sustain circadian locomotor activity (80,81).…”

Prokineticins are neuroprotective in models of cerebral ischemia and ischemic tolerance in vitro

“…These two peptides are highly conserved across species (LeCouter et al, 2004;Giannini et al, 2009) and activate two highly homologous receptors, prokineticin receptor 1 (PKR1) and PKR2 (Negri and Lattanzi, 2011), which are coupled to a variety of G proteins and hence to intracellular Ca 2þ mobilization and activation of the ERK1/2 and Akt pathways (Lin et al, 2002;Masuda et al, 2002;Soga et al, 2002). Prokineticins (especially PK2) and their receptors are largely expressed in CNS (Cheng et al, 2006) and regulate multiple biological functions in the CNS including hyperalgesia (Mollay et al, 1999), neurogenesis in the olfactory bulb (Ng et al, 2005), neuronal survival (Melchiorri et al, 2001) and inflammation (Martucci et al, 2006). Recent studies have implicated PK2 in human diseases such as, for example, Kallmann syndrome, which can be determined by loss-offunction mutations in the gene encoding for PK2 (Pitteloud et al, 2007) or CNS autoimmune demyelination, in which PK2 has been identified as a critical immune regulator (Abou-Hamdan et al, 2015).…”

Prokineticin 2 Is a Target Gene of Proneural Basic Helix-Loop-Helix Factors for Olfactory Bulb Neurogenesis

“…In the adult mouse brain, PK2 is expressed abundantly in the suprachiasmatic nucleus (SCN) and the GCL and PGL in the OB (18,19,21 In this study, we examine the regulation of the PK2 gene by the proneural bHLH factors Ngn1 and MASH1 in the embryonic and postnatal mouse OB. We found that the expressions of these genes overlap in several populations of OB neurons, and the expression of the PK2 gene is reduced in Ngn1 and MASH1 mutant mice.…”

“…In the adult mouse brain, PK2 is expressed abundantly in the suprachiasmatic nucleus (SCN) and the GCL and PGL in the OB (18,19,21). In the SCN, a heterodimer of CLOCK and BMAL1, two bHLH factors, regulates the rhythmic expression of the PK2 gene by binding to E-box elements on the PK2 promoter (18).…”