No abstract

In rodents, the melatonin production by the pineal gland is controlled through adrenergic signaling from the suprachiasmatic nuclei and regulation of the principal enzyme in its synthesis, arylalkylamine-N-acetyltransferase (AANAT). In the present study, we identified increased isoprenaline-induced aa-nat expression and nocturnal AANAT activity in the pineal glands in response to the silencing of the signal transducer and activator of transcription 3 (STAT3) with siRNA or STAT3 inhibitors WP1066 and AZD1480. This AANAT activity enhancement in vivo did not interfere with light-induced AANAT suppression. Systemic or in vitro lipopolysaccharide (LPS) administration markedly increased Stat3 expression and STAT3 phosphorylation, but it did not significantly affect AANAT expression or activity. Simultaneous LPS administration and Stat3 silencing enhanced the aa-nat transcription and AANAT activity to a similar extent as Stat3 inhibition without LPS co-administration. Furthermore, we describe the circadian rhythmicity in Stat3 expression and the phosphorylated form of STAT3 protein in the rat pineal gland. Our data suggest that the higher nocturnal endogenous level of STAT3 in the pineal gland decelerates or hampers the process of NA-induced AANAT activation or affects the AANAT enzyme stability.

Adar2-/- mice are a widely used model to study the physiological consequences of reduced RNA editing. These mice are viable only when the Q/R editing site of the Gria2 subunit of the AMPA receptor is constitutively mutated to the codon for arginine, and Gria2R/R mice often serve as the sole control for Adar2-/- mice. The aim of our study was to investigate whether ADAR2 inactivity and the Gria2R/R phenotype affect the rhythmicity of the pattern of circadian clock genes and the expression of Gria1 and Gria2 subunits in the suprachiasmatic nucleus (SCN), hippocampus, parietal cortex and liver. Our data show that Gria2R/R mice completely lost circadian rhythmicity in the hippocampus compared to Adar2-/- mice. Compared to C57BL/6J mice, expression profiles in hippocampus and parietal cortex of Gria2R/R mice differ to the same extent as in Adar2-/-. These data suggest that the natural gradual increase in the editing of the Q/R site of the Gria2 subunit postnatally may be important for the development of circadian clockwork in some brain structures, and the use of Gria2R/R mice as the only control to Adar2-/- mice in the hippocampus- and parietal cortex- dependent experiments should therefore be considered.