Dataset Information

Long-term consequences of chronic fluoxetine exposure on the expression of myelination-related genes in the rat hippocampus.

ABSTRACT: The selective serotonin reuptake inhibitor (SSRI) fluoxetine is widely prescribed for the treatment of symptoms related to a variety of psychiatric disorders. After chronic SSRI treatment, some symptoms remediate on the long term, but the underlying mechanisms are not yet well understood. Here we studied the long-term consequences (40 days after treatment) of chronic fluoxetine exposure on genome-wide gene expression. During the treatment period, we measured body weight; and 1 week after treatment, cessation behavior in an SSRI-sensitive anxiety test was assessed. Gene expression was assessed in hippocampal tissue of adult rats using transcriptome analysis and several differentially expressed genes were validated in independent samples. Gene ontology analysis showed that upregulated genes induced by chronic fluoxetine exposure were significantly enriched for genes involved in myelination. We also investigated the expression of myelination-related genes in adult rats exposed to fluoxetine at early life and found two myelination-related genes (Transferrin (Tf) and Ciliary neurotrophic factor (Cntf)) that were downregulated by chronic fluoxetine exposure. Cntf, a neurotrophic factor involved in myelination, showed regulation in opposite direction in the adult versus neonatally fluoxetine-exposed groups. Expression of myelination-related genes correlated negatively with anxiety-like behavior in both adult and neonatally fluoxetine-exposed rats. In conclusion, our data reveal that chronic fluoxetine exposure causes on the long-term changes in expression of genes involved in myelination, a process that shapes brain connectivity and contributes to symptoms of psychiatric disorders.

SUBMITTER: Kroeze Y

PROVIDER: S-EPMC5068807 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Long-term consequences of chronic fluoxetine exposure on the expression of myelination-related genes in the rat hippocampus.

Kroeze Y Y Peeters D D Boulle F F Pawluski J L JL van den Hove D L A DL van Bokhoven H H Zhou H H Homberg J R JR

Translational psychiatry 20150922

The selective serotonin reuptake inhibitor (SSRI) fluoxetine is widely prescribed for the treatment of symptoms related to a variety of psychiatric disorders. After chronic SSRI treatment, some symptoms remediate on the long term, but the underlying mechanisms are not yet well understood. Here we studied the long-term consequences (40 days after treatment) of chronic fluoxetine exposure on genome-wide gene expression. During the treatment period, we measured body weight; and 1 week after treatme ...[more]

PMID: 26393488

Similar Datasets

Project description:Both the mechanism of action and the factors determining the behavioral response to antidepressants are unknown. It has been shown that antidepressant treatment promotes the proliferation and survival of hippocampal neurons via enhanced serotonergic signaling, but it is still unclear whether hippocampal neurogenesis is responsible for the behavioral response to antidepressants. Furthermore, a large subpopulation of patients fails to respond to antidepressant treatment due to presumed underlying genetic factors. In the present study, we have used the phenotypic and genotypic variability of inbred mouse strains to show that there is a genetic component to both the behavioral and neurogenic effects of chronic fluoxetine treatment, and that this antidepressant induces an increase in hippocampal cell proliferation only in the strains that also show a positive behavioral response to treatment. The behavioral and neurogenic responses are associated with an upregulation of genes known to promote neuronal proliferation and survival. These results suggest that inherent genetic predisposition to increased serotonin-induced neurogenesis is a determinant of antidepressant efficacy. Experiment Overall Design: Male DBA/2J, age 3-5 weeks, were obtained from The Jackson Laboratory (Bar Harbor, ME) and maintained on a 12:12 light:dark cycle with lights on at 0700 hours. Following at least one week of acclimation, mice were provided with either untreated or fluoxetine-treated drinking water, available ad libitum. Fluoxetine-HCl was obtained from Spectrum Chemicals (Gardena, CA). Differences in daily water consumption were previously determined by measuring water intake for three weeks from at least 12 mice (6.4 mL (+/- .58 mL) per day). We also determined the average weight at 10 weeks of age (25.5 g +/- 1.4 g), and used this information to dilute fluoxetine in the water in order to provide a daily dosage of 0 or 18 mg/kg/mouse. Experiment Overall Design: Mice were 8-12 weeks of age at the time of behavioral testing, which was performed during the light phase between 1300h and 1600h. Behavioral despair was measured using a mouse Tail Suspension apparatus from Med Associates (Georgia, VT). Experiment Overall Design: Individual bilateral hippocampii from 21-day-treatment 0 and 18 mg/kg/day DBA/2J mice were homogenized in 500 Âµl TRIzol using a QIAgen Tissuelyser (15 minutes at 30 Hz, QIAgen, Chatsworth, CA). RNA was extracted by phenol-chloroform phase separation and further processed using the RNAeasy miniprep kit (QIAgen). For each treatment group of 12 animals, separate RNA pools were made using hippocampal RNA from 6 mice per pool. These biological replicates were processed separately through the entirety of the microarray procedure. Five Âµg of total RNA from each pool was used as a template to synthesize complementary DNA (cDNA) and biotinylated cRNA (Enzo kit, Affymetrix, Santa Clara, CA) using standard Affymetrix protocols. cRNA was hybridized to Affymetrix GeneChip Mouse Genome 430 2.0 Array. Data were analyzed using ArrayAssist software (Stratagene, La Jolla, CA) and normalized with the GCRMA algorithm. A probeset had to obtain a minimal intensity value 100 to be considered as detecting expression above background. Therefore, any probeset that failed to meet this cutoff was removed from the analysis. Ratios of intensity differences were generated and genes showing at least a two-fold difference between experimental conditions were identified for further analysis.

Project description:PurposeResistance to antibiotics is a major problem of public health. One of the alternative therapies is silver - more and more popular because of nanotechnology development and new possibilities of usage. As a component of colloid, powder, cream, bandages, etc., nanosilver is often recommended to treat the multidrug-resistant pathogens and we can observe its overuse also outside of the clinic where different physicochemical forms of silver nanoformulations (e.g. size, shape, compounds, surface area) are introduced. In this research, we described the consequences of long-term bacteria exposure to silver nanoformulations with different physicochemical properties, including changes in genome and changes of bacterial sensitivity to silver nanoformulations and/or antibiotics. Moreover, the prevalence of exogenous resistance to silver among multidrug-resistant bacteria was determined.Materials and methodsGram-negative and Gram-positive bacteria strains are described as sensitive and multidrug-resistant strains. The sensitivity of the tested bacterial strains to antibiotics was carried out with disc diffusion methods. The sensitivity of bacteria to silver nanoformulations and development of bacterial resistance to silver nanoformulations has been verified via determination of the minimal inhibitory concentrations. The presence of sil genes was verified via PCR reaction and DNA electrophoresis. The genomic and phenotypic changes have been verified via genome sequencing and bioinformatics analysis.ResultsBacteria after long-term exposure to silver nanoformulations may change their sensitivity to silver forms and/or antibiotics, depending on the physicochemical properties of silver nanoformulations, resulting from phenotypic or genetic changes in the bacterial cell. Finally, adaptants and mutants may become more sensitive or resistant to some antibiotics than wild types.ConclusionApplication of silver nanoformulations in the case of multiple resistance or multidrug-resistant bacterial infection can enhance or decrease their resistance to antibiotics. The usage of nanosilver in a clinic and outside of the clinic should be determined and should be under strong control. Moreover, each silver nanomaterial should be considered as a separate agent with a potential different mode of antibacterial action.

Dataset Information

Long-term consequences of chronic fluoxetine exposure on the expression of myelination-related genes in the rat hippocampus.

Publications

Long-term consequences of chronic fluoxetine exposure on the expression of myelination-related genes in the rat hippocampus.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets