S100B interacts with the serotonin 5-HT7 receptor to regulate a depressive-like behavior

Area of Science:

• Neuroscience
• Molecular Biology
• Psychiatry

Background:

• The serotonin 5-HT7 receptor (5-HT7) is a potential target for psychiatric medications.
• Its blockade is linked to antidepressant effects in preclinical and human studies.

Purpose of the Study:

• To investigate the interaction between S100B and the 5-HT7 receptor.
• To determine the role of S100B in regulating cyclic AMP (cAMP) pathways and its impact on behavior.

Main Methods:

• Identified S100B as a 5-HT7 interacting partner.
• Assessed S100B's regulation of cAMP accumulation in cell cultures and mouse brains.
• Utilized S100B transgenic mice and the forced swim test (FST).
• Administered 5-HT7 antagonist SB269970.

Main Results:

• S100B negatively regulates inducible cAMP accumulation.
• S100B overexpression leads to region-specific cAMP dysregulation in vivo.
• S100B transgenic female mice exhibit higher frontal cortex cAMP levels and depressive-like behavior in the FST.
• 5-HT7 blockade with SB269970 normalized FST behavior in these mice.

Conclusions:

• S100B influences behavioral despair in female mice via functional interaction with the 5-HT7 receptor.
• S100B acts as a cAMP-regulatory protein in astrocytes and the murine frontal cortex.
• Further research is needed to link the 5-HT7-associated and cAMP-regulatory functions of S100B.