Cyclic ADP-ribose and heat regulate oxytocin release via CD38 and TRPM2 in the hypothalamus during social or psychological stress in mice

摘要: Hypothalamic oxytocin (OT) is released into the brain by cyclic ADP-ribose (cADPR) with or without depolarizing stimulation. Previously, we showed that intracellular free calcium concentration ([Ca2+]i) seems to trigger OT release can be elevated -NAD+, cADPR, and ADP in mouse oxytocinergic neurons. As these -NAD+ metabolites activate warm-sensitive TRPM2 cation channels, when incubation temperature increased, [Ca2+]i hypothalamic neurons elevated. However, it has not been determined whether facilitated heat vitro hyperthermia vivo combination cADPR. Furthermore, examined CD38 exert their functions on during stress stress-induced relation anxiolytic roles social behaviors of under conditions. Here, report from isolated hypothalami male mice culture was enhanced extracellular application cADPR increasing 35°C 38.5°C, simultaneous stimulation a greater effect. This inhibited cADPR-dependent ryanodine receptor inhibitor nonspecific inhibitor. The suppressed hypothalamus knockout CD38- TRPM2-knockdown mice. In course experiments, noted differed markedly between individual group housing. That is, received cage-switch eliminated due subclass, significantly higher levels were found subordinates compared ordinates. exposed anxiety an open field, cerebrospinal fluid (CSF) level increased transiently at 5 minutes after exposure, rectal also 36.6°C 37.8°C. CSF lipopolysaccharide-induced fever (+0.8°C) than those control mRNA immunoreactivities subordinate stress. These results cADPR/CD38 heat/TRPM2 are co-regulators secretion suggested potential therapeutic targets for psychiatric diseases caused