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• W3110305624 endingPage "1694" @default.
• W3110305624 startingPage "1683" @default.
• W3110305624 abstract "Mood-related disorders have a high prevalence among children and adolescents, posing a public health challenge, given their adverse impact on these young populations. Treatment with the selective serotonin reuptake inhibitor fluoxetine (FLX) is the first line of pharmacological intervention in pediatric patients suffering from affect-related illnesses. Although the use of this antidepressant has been deemed efficacious in the juvenile population, the enduring neurobiological consequences of adolescent FLX exposure are not well understood. Therefore, we explored for persistent molecular adaptations, in the adult hippocampus, as a function of adolescent FLX pretreatment. To do this, we administered FLX (20 mg/kg/day) to male C57BL/6 mice during adolescence (postnatal day [PD] 35-49). After a 21-day washout period (PD70), whole hippocampal tissue was dissected. We then used qPCR analysis to assess changes in the expression of genes associated with major intracellular signal transduction pathways, including the extracellular signal-regulated kinase (ERK), the phosphatidylinositide-3-kinase (PI3K)/AKT pathway, and the wingless (Wnt)-dishevelled-GSK3β signaling cascade. Our results show that FLX treatment results in long-term dysregulation of mRNA levels across numerous genes from the ERK, PI3K/AKT, and Wnt intracellular signaling pathways, along with increases of the transcription factors CREB, ΔFosB, and Zif268. Lastly, FLX treatment resulted in persistent increases of transcripts associated with cytoskeletal integrity (β-actin) and caspase activation (DIABLO), while decreasing genes associated with metabolism (fucose kinase) and overall neuronal activation (c-Fos). Collectively, these data indicate that adolescent FLX exposure mediates persistent alterations in hippocampal gene expression in adulthood, thus questioning the safety of early-life exposure to this antidepressant medication." @default.
• W3110305624 created "2020-12-07" @default.
• W3110305624 creator A5026699928 @default.
• W3110305624 creator A5027447945 @default.
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• W3110305624 creator A5056682052 @default.
• W3110305624 date "2020-11-25" @default.
• W3110305624 modified "2023-10-14" @default.
• W3110305624 title "Adolescent Fluoxetine Exposure Induces Persistent Gene Expression Changes in the Hippocampus of Adult Male C57BL/6 Mice" @default.
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• W3110305624 doi "https://doi.org/10.1007/s12035-020-02221-9" @default.
• W3110305624 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7933079" @default.
• W3110305624 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33241493" @default.
• W3110305624 hasPublicationYear "2020" @default.
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