Objective The rostral anterior cingulate cortex （rACC） is implicated in processing the emotional component of pain. N-methyl-D-aspartate receptors （NMDARs） are highly expressed in the rACC and mediate painrelated affect by activating a signaling pathway that involves cyclic adenosine monophosphate （cAMP）/protein ki- nase A （PKA） and/or extracellular regulated kinase （ERK）/cAMP-response element-binding protein （CREB）. The present study investigated the contributions of the NMDAR glycine site and GluN2B subunit to the activation of ERK and CREB both in vitro and in vivo in rat rACC. Methods Immunohistochemistry and Western blot analy- sis were used to separately assess the expression of phospho-ERK （pERK） and phospho-CREB （pCREB） in vitro and in vivo. Double immunostaining was also used to determine the colocalization of pERK and pCREB. Results Both bath application of NMDA in brain slices in vitro and intraplantar injection of formalin into the rat hindpaw in vivo induced significant up-regulation of pERK and pCREB in the rACC, which was inhibited by the NMDAR antago- nist DL-2-amino-5-phospho-novaleric acid. Selective blockade of the NMDAR GluN2B subunit and the glycine- binding site, or degradation of endogenous D-serine, a co-agonist for the glycine site, significantly decreased the up- regulation of pERK and pCREB expression in the rACC. Further, the activated ERK predominantly colocalized with CREB. Conclusion Either the glycine site or the GluN2B subunit of NMDARs participates in the phosphorylation of ERK and CREB induced by bath application of NMDA in brain slices or hindpaw injection of 5% formalin in rats, and these might be fundamental molecular mechanisms underlying pain affect.
Hong CaoWen-Hua RenMu-Ye ZhuZhi-Qi ZhaoYu-Qiu Zhang
In this study,we investigated the role ofβ-arrestin-2in alcohol preference using the two-bottle choice and conditioned place preference procedures in wild-type（WT）andβ-arrestin-2 knockout（KO）mice.Locomotion and righting reflex tests were performed to test alcohol sensitivity.The possible molecular signals regulated byβ-arrestin-2 were analyzed by Western blot.We found thatβ-arrestin-2 KO mice showed a marked increase in voluntary alcohol consumption without significant differences in preference for saccharin or aversion to quinine.These animals also exhibited higher conditioned place preference scores for alcohol than WT mice.Meanwhile,KO mice showed reduced sensitivity to alcohol and increased blood alcohol clearance.Furthermore,after the free consumption of alcohol,the activities of protein kinase B and glycogen synthase kinase 3β（GSK3β）increased in the dorsal striatum of WT mice,but not in KO mice,which showed high basal activity of Akt in the dorsal striatum.These results suggest thatβ-arrestin-2 negatively regulates alcohol preference and reward,likely through regulating the activation of signaling pathways including Akt/GSK3βin the dorsal striatum.
The circadian clock and sleep are essential for human physiology and behavior; deregulation of circadian rhythms impairs health and performance. Circadian clocks and sleep evolved to adapt to Earth's environment, which is characterized by a 24-hour light–dark cycle. Changes in gravity load, lighting and work schedules during spaceflight missions can impact circadian clocks and disrupt sleep, in turn jeopardizing the mood, cognition and performance of orbiting astronauts. In this review, we summarize our understanding of both the influence of the space environment on the circadian timing system and sleep and the impact of these changes on astronaut physiology and performance.
