Chronic Fluoxetine Treatment Changes S100B Expression During Postnatal Rat Brain Development

Abstract

Background: Fluoxetine, a selective serotonin reuptake inhibitor, is approved for treatment of childhood depression. In rats, fluoxetine influences neuronal development, but it is unclear whether it also influences glia development. S100B is a gliaderived calcium-binding protein, which may influence the development of serotonergic fibers and, vice versa, serotonin may influence the expression of S100B. Objectives: The purpose of this study was to investigate whether fluoxetine treatment influences the expression of S100B during postnatal development, and whether potential changes are regionally dependent upon the time frame of drug administration. Methods: S100B gene expression and S100B protein expression in three different brain regions (frontal cortex, hippocampus, and striatum) were studied by real-time polymerase chain reaction (PCR) and immunohistochemistry, respectively. First, a short-term effect, 24 hours after a 14 day fluoxetine treatment (5 mg/kg/bw s.c.) of rats either from postnatal day (PD) 1 to 15, 21 to 35, or 50 to 64, was investigated. Then, the same treatment was used to analyze S100B gene and protein levels at PD 90 (long-term effect). Results: At PD 90, a significant increase of gene and protein expression was observed in all regions if rats were treated during PDs 21-35, whereas treatment during other periods had no long-term effects. A short-term effect 24 hours after fluoxetine treatment was found for almost all development stages and regions, demonstrated by a significant increase of S100B. Conclusions: These results support recent research indicating a highly drug-sensitive period (i.e., periadolescence) of rat brain development. Therefore, further clinical studies should be performed to clarify whether such a sensitive period also exists in children.

Peripheral administration of lactate produces antidepressant-like effects

“… 51 In contrast, chronic treatment with the selective serotonin reuptake inhibitor antidepressant fluoxetine increases S100β expression in the rodent hippocampus. 52 , 53 Our data showing that l -lactate administration increases S100β expression in the hippocampus of animals subjected to the open-space FST ( Figure 4c ) are in line with these observations, and suggest that S100β may be a mediator of the chronic antidepressant-like effects of l -lactate.…”

The S100B story: from biomarker to active factor in neural injury

“…It may be relevant in this respect that the antidepressant fluoxetine has been shown to increase hippocampal and CSF levels of both the protein and its receptor in rats exposed to chronic mild stress, reversing the decrease induced by stress treatment (Rong et al 2010). Treatment with fluoxetine has also been reported to increase S100B levels in the hippocampus, frontal cortex and striatum, and S100B release from raphes (Manev et al 2001;Akhisaroglu et al 2003;Baudry et al 2010;Bock et al 2013).…”

Effect of Early-Life Fluoxetine on Anxiety-Like Behaviors in BDNF Val66Met Mice

“…Fluoxetine, administered to rats in a peri-adolescent timeframe (P21–35) results in significant increases in S100B in multiple brains regions that persisted into adulthood (65). In vitro and in vivo studies indicate that S100B has trophic effects on serotonergic neurons (50, 66, 67).…”