S100B interacts with the serotonin 5-HT7 receptor to regulate a depressive-like behavior.
The serotonin 5-HT7 receptor (5-HT7) is an emerging target for psychiatric pharmacotherapy. Recent observations in rodent models and humans suggest that its blockade mediates antidepressant efficacy. In the present study, we identify the Ca(2+)-binding protein S100B as an interacting partner of 5-HT7 and show that S100B negatively regulates inducible cyclic AMP (cAMP) accumulation in transfected HeLa cells and mouse cortical astrocytes. Overexpression of S100B causes brain region-specific dysregulation of the cAMP pathway in vivo, such that concentrations of cAMP in the frontal cortex are higher in S100B transgenic female mice compared to wild-types. Finally, S100B transgenic female mice show depressive-like behavior in the forced swim test (FST) and pharmacological blockade of 5-HT7 with SB269970 normalizes FST behavior. Taken together, our results show that S100B affects behavioral despair in female mice through functional interaction with the 5-HT7 receptor. Furthermore, we identify S100B as a cAMP-regulatory protein in cultured astrocytes and the murine frontal cortex. Future experiments will clarify whether there is a direct link between the 5-HT7-associated and cAMP-regulatory actions of S100B.
Center for Molecular Medicine, Department of Clinical Neuroscience, Karolinska Institute, 17176 Stockholm, Sweden. Electronic address: nikolas.stroth@ki.se.
Nikolas
N
Stroth
Center for Molecular Medicine, Department of Clinical Neuroscience, Karolinska Institute, 17176 Stockholm, Sweden.
Per
P
Svenningsson
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D003863:Depression / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008958:Models, Molecular; D018377:Neurotransmitter Agents / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism*; D064568:S100 Calcium Binding Protein beta Subunit / Q000235:genetics / Q000378:metabolism*; D013550:Swimming / Q000523:psychology
D018377:Neurotransmitter Agents; D011985:Receptors, Serotonin; D064568:S100 Calcium Binding Protein beta Subunit; C579159:S100b protein, mouse; C104425:serotonin 7 receptor; D005576:Colforsin; D000242:Cyclic AMP
Behavior; Cyclic AMP; Depression; Frontal cortex; S100B; Serotonin 5-HT(7) receptor