Secretion of S100B, an astrocyte-derived neurotrophic protein, is stimulated by fluoxetine via a mechanism independent of serotonin.
S100B is a calcium-binding protein, produced and secreted by astrocytes, which has a putative paracrine neurotrophic activity. Clinical studies have suggested that peripheral elevation of this protein is positively correlated with a therapeutic antidepressant response, particularly to selective serotonin reuptake inhibitors (SSRIs); however, the mechanism underlying this response remains unclear. Here, we measured S100B secretion directly in hippocampal astrocyte cultures and hippocampal slices exposed to fluoxetine and observed a significant increment of S100B release in the presence of this SSRI, apparently dependent on protein kinase A (PKA). Moreover, we found that serotonin (possibly via the 5HT1A receptor) reduces S100B secretion and antagonizes the effect of fluoxetine on S100B secretion. These data reinforce the effect of fluoxetine, independently of serotonin and serotonin receptors, suggesting a putative role for S100B in depressive disorders and suggesting that other molecular targets may be relevant for antidepressant activity.
Tramontina
Ana Carolina
AC
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos, 2600- Anexo, 90035-003, Porto Alegre, Brazil.
Tramontina
Francine
F
Bobermin
Larissa D
LD
Zanotto
Caroline
C
Souza
Daniela F
DF
Leite
Marina C
MC
Nardin
Patrícia
P
Gottfried
Carmem
C
Gonçalves
Carlos-Alberto
CA
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005473:Fluoxetine / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology / Q000502:physiology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D005473:Fluoxetine; D009414:Nerve Growth Factors; D011985:Receptors, Serotonin; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; C579158:S100b protein, rat