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

Area of Science:

• Neuroscience
• Biochemistry
• Pharmacology

Background:

• BST-1 (CD157) and CD38 are ecto-enzymes with ADP-ribosyl cyclase activity.
• They produce cyclic ADP-ribose, a key ligand for ryanodine receptors (RyRs).
• Previous studies showed Bst1 knockout mice exhibit depression-like symptoms, but Cd38 knockout mice do not.

Purpose of the Study:

• To clarify the differential roles of BST-1 and CD38 in depression-like behaviors.
• To investigate the impact of these enzymes on calcium (Ca2+) signaling pathways.
• To understand the specific contributions of BST-1 and CD38 to RyR expression and function.

Main Methods:

• Behavioral tests were performed on wild-type, Bst1 knockout, Cd38 knockout, and double knockout mice.
• Calcium (Ca2+) signaling was evaluated in all mouse models.
• RyR expression levels were assessed in the different knockout groups.

Main Results:

• Bst1 knockout mice exhibited depression-like symptoms and increased RyR expression.
• Cd38 knockout mice did not show depression-like symptoms.
• Double knockout mice (lacking both BST-1 and CD38) did not exhibit depression-like symptoms, and their elevated RyR expression was normalized.

Conclusions:

• CD38 may act as an inducer of depression-like symptoms.
• BST-1 appears to have a suppressive role in depression-like behaviors.
• The interplay between BST-1 and CD38 is crucial for regulating RyR-mediated calcium signaling and depressive phenotypes.