Proteomics and Biomarkers, Max Planck Institute of Psychiatry, Munich 80804, Germany.
Ludwig-Maximilians-Universität, Chair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, Munich 80336, Germany.
Zool Res. 2023 Jan 18;44(1):30-42. doi: 10.24272/j.issn.2095-8137.2022.196.
Fluoxetine (Prozac™) is the only antidepressant approved by the US Food and Drug Administration (FDA) for the treatment of major depressive disorder (MDD) in children. Despite its considerable efficacy as a selective serotonin reuptake inhibitor, the possible long-term effects of fluoxetine on brain development in children are poorly understood. In the current study, we aimed to delineate molecular mechanisms and protein biomarkers in the brains of juvenile rhesus macaques () one year after the discontinuation of fluoxetine treatment using proteomic and phosphoproteomic profiling. We identified several differences in protein expression and phosphorylation in the dorsolateral prefrontal cortex (DLPFC) and cingulate cortex (CC) that correlated with impulsivity in animals, suggesting that the GABAergic synapse pathway may be affected by fluoxetine treatment. Biomarkers in combination with the identified pathways contribute to a better understanding of the mechanisms underlying the chronic effects of fluoxetine after discontinuation in children.
氟西汀（Prozac™）是美国食品和药物管理局（FDA）唯一批准用于治疗儿童重度抑郁症（MDD）的抗抑郁药。尽管它作为一种选择性 5-羟色胺再摄取抑制剂具有相当的疗效，但氟西汀对儿童大脑发育的可能长期影响还知之甚少。在本研究中，我们使用蛋白质组学和磷酸化蛋白质组学分析，旨在描绘幼年恒河猴（）停止氟西汀治疗一年后大脑中的分子机制和蛋白质生物标志物。我们在背外侧前额叶皮层（DLPFC）和扣带皮层（CC）中发现了几种与动物冲动性相关的蛋白质表达和磷酸化差异，表明 GABA 能突触通路可能受到氟西汀治疗的影响。结合鉴定出的通路的生物标志物有助于更好地理解氟西汀在儿童停药后慢性作用的机制。
