The depression-like state in Bst1/Cd157 knock-out mice is attenuated by double knock-out with Cd38

BST-1/CD157 and CD38 are ecto-enzymes with ADP-ribosyl cyclase activity that produce cyclic ADP-ribose, which is a ligand for ryanodine receptors (RyRs). Bst1 knockout (KO), but not Cd38KO, mice exhibited depression-like symptoms. However, the differential roles of ADP-ribosyl cyclases in depression-like symptoms have not been clarified. Behavioral tests for depression were conducted and Ca²⁺signaling in Bst1KO, Cd38KO, Cd38Bst1 double-KO (DKO), and wild-type mice was evaluated. DKO mice did not show depression-like symptoms; increased expression of RyRs seen in Bst1KO mice was corrected. This suggests that CD38 may be a factor that induces depression and that BST-1 may suppress it.