Expression of ectonucleotidases in the prosencephalon of melatonin-proficient C3H and melatonin-deficient C57Bl mice: spatial distribution and time-dependent changes

Abstract

Extracellular purines (ATP, ADP, AMP and adenosine) are important signaling molecules in the CNS. Levels of extracellular purines are regulated by enzymes located at the cell surface referred to as ectonucleotidases. Time-dependent changes in their expression could profoundly influence the availability of extracellular purines and thereby purinergic signaling. Using radioactive in situ hybridization, we analyzed the mRNA distribution of the enzymes NTPDase1, -2 and -3 and ecto-5'-nucleotidase in the prosencephalon of two mouse strains: melatonin-proficient C3H and melatonin-deficient C57Bl. The mRNAs of these enzymes were localized to specific brain regions, such as hippocampus, striatum, medial habenula and ventromedial hypothalamus. NTPDase3 expression was more widely distributed than previously thought. All ectonucleotidases investigated revealed a prominent time-dependent expression pattern. In C3H, the mRNA expression of all four enzymes gradually increased during the day and peaked during the night. In contrast, in C57Bl, ecto-5'-nucleotidase expression peaked at the beginning of the day and gradually decreased to trough levels at night. Recording of locomotor activity revealed higher daytime activity of C57Bl than of C3H. Our results indicate that the expression of ectonucleotidases varies according to time and genotype and suggest that melatonin exerts modulatory effects associated with different regulations of purinergic signaling in the brain. These findings provide an important basis for further examination of the complexity of the purinergic system in the brain.

Seasonal Variations of Locomotor Activity Rhythms in Melatonin-Proficient and -Deficient Mice under Seminatural Outdoor Conditions

“…In the C3H group, there was higher activity on short, warm nights, while the C57Bl group did not show any trend at all. Notably, the C3H mice were more active under the outdoor conditions as compared with the C57Bl animals, whereas, under laboratory conditions, the total activity levels of the 2 strains did not differ (Homola et al, 2015; Wicht et al, 2014).…”

“…Much of our knowledge of the circadian system and its entrainment (i.e., the responses to abiotic cues such as light or temperature, as well as masking effects, entrainment, chronotype, and rhythm stability) have been studied almost exclusively in the laboratory under standardized conditions (Homola et al, 2015; Mrosovsky, 1996; Pfeffer et al, 2012; Refinetti, 2002; Refinetti, 2004; von Gall et al, 1998; Wicht et al, 2014).…”

Melatonin Receptor 1 Deficiency Affects Feeding Dynamics and Pro-Opiomelanocortin<b> </b>Expression in the Arcuate Nucleus and Pituitary of Mice

“…Actograms and activity profiles were created using Clocklab software (Actimetrics, Wilmette, Ill., USA) as described [34,35] . The daytime activity was expressed in percent of the total/daily (24 h) activity as described [34,36] .…”

The P2Y1 receptor-mediated leukocyte adhesion to endothelial cells is inhibited by melatonin

“…Recently, Homola and co-workers [21] suggested that melatonin regulates the expression of brain ectonucleotidases; therefore, the anti-inflammatory role of melatonin may involve the regulation of signaling via P2 receptors, including endothelial P2Y 1 R. However, no studies have addressed the effect of melatonin on purinergic P2Y receptor signaling. Here, we show that melatonin in the nM range of concentration inhibited the P2Y 1 R-induced leukocyte adhesion to rat endothelial cells and TNF-α production in vitro, suggesting melatonin as a novel modulator of purinergic signaling.…”