Date of Award
Master of Arts
Sergio D. Iñiguez
Mood-related disorders, including depression and anxiety, are prevalent among children and adolescents. This poses 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. For this reason, 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). Twenty-one days later (PD70), whole hippocampal tissue was dissected. We then incorporated the quantitative real-time reverse transcription polymerase chain reaction (qPCR) approach 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-GSK3B 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 induces persistent alterations in hippocampal gene expression in adulthood, thus, questioning the safety of early-life exposure to this antidepressant medication.
Recieved from ProQuest
Themann, Anapaula, "Long-Term Effects of Adolescent Fluoxetine Exposure on Hippocampal Gene Expression in Male C57BL/6 Mice" (2021). Open Access Theses & Dissertations. 3455.