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首页> 外文期刊>Neuropharmacology >Perinatal fluoxetine prevents the effect of pre-gestational maternal stress on 5-HT in the PFC, but maternal stress has enduring effects on mPFC synaptic structure in offspring
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Perinatal fluoxetine prevents the effect of pre-gestational maternal stress on 5-HT in the PFC, but maternal stress has enduring effects on mPFC synaptic structure in offspring

机译：Perinatal Flyoxetine可以防止PFC中的5-HE在5-HT中的妊娠前母体应激的影响，但母体应力对后代的MPFC突触结构具有持久的影响

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Abstract Maternal affective disorders are frequently treated with selective serotonin reuptake inhibitor medications (SSRIs); with up to 10% of women being prescribed these medications during pregnancy. Infant development depends on the early serotonergic environment, which is altered by perinatal SSRIs, raising concern about how these medications affect neural outcomes. While clinical and preclinical research suggests an impact of SSRIs on the developing brain, more research is needed to determine the effects on neuroplasticity, the serotonergic system, and the hypothalamic-pituitary-adrenal axis in neural regions mediating behavior. The current work investigated the effects of the SSRI, fluoxetine, on the serotonergic system in the prefrontal cortex (PFC) during pre-adolescence, and changes to synaptic markers and glucocorticoid receptor density in the cingulate cortex (medial PFC) of pre-adolescent and adult Sprague-Dawley male and female rats. To model aspects of Perinatal Depression and maternal anxiety, pre-gestational maternal stress was used resulting in male and female offspring from 4 groups: 1) control, 2) perinatal fluoxetine exposed, 3) pre-gestational maternal stress exposed, and 4) pre-gestational maternal stress?+?fluoxetine. Perinatal fluoxetine prevented the effects of maternal stress on 5-HT levels and 5-HT turnover ratio in the PFC of pre-adolescent offspring, particularly in females. However, pre-gestational stress reduced synaptophysin and PSD-95 densities in the cingulate cortex, effects that were more pronounced in males. Interestingly, perinatal fluoxetine exposure reduced GR density in adult males in this same brain area. Together, results show differential effects of perinatal SSRIs and pre-gestational maternal stress on neurodevelopment in the PFC of males and females. Highlights ? Perinatal SSRIs prevent the effects of maternal stress on preadolescent 5-HT in the PFC. ? Pre-gestational stress, but not perinatal SSRIs, reduce synaptic markers in offspring cingulate cortex. ? Perinatal SSRIs reduce glucocorticoid receptor density in the cingulate cortex, particularly in males. ? Perinatal SSRIs effects are altered by pre-gestational maternal stress, offspring age and sex/gender.
机译：摘要母体情感障碍经常用选择性血清素再摄取抑制剂药物（SSRIS）治疗;在怀孕期间，高达10％的女性在怀孕期间进行了这些药物。婴儿发展取决于早期的血清奈良加尔环境，这被围产期SSRIS改变，提高了这些药物如何影响神经结果。虽然临床和临床前研究表明SSRIS对发育大脑的影响，但需要更多的研究来确定神经构造，血清奈奈治疗和神经区域中下丘脑垂体肾上腺轴的影响。目前的作品研究了SSRI，Flyoxetine，在前额叶皮层（PFC）中的血清酰胺能系统中的效果，以及对前青少年和胶凝皮质（内侧PFC）中的突触标志物和糖皮质激素受体密度的变化成人sprague-dawley男女鼠。为了模拟围产期抑郁和母亲焦虑的方面，使用预妊娠母体压力，导致4组的男性和女性后代：1）对照，2）潜水氟西汀暴露，3）预妊娠母体应力暴露，4）前 - 孕产妇胁迫？+？氟西汀。围产期氟西汀阻止了母体胁迫对青少年前后代PFC的5-HT水平和5-HT周转率的影响，特别是在女性中。然而，妊娠期胁迫降低了突触皮质和PSD-95密度在铰接皮质中，在雄性中更加明显的效果。有趣的是，围产期氟西汀暴露在同一脑面积中的成年雄性中的GR密度降低。在一起，结果表明围产期SSRIS和妊娠前母体压力对雄性和女性PFC神经发育的差异影响。强调 ？围产期SSRI防止母体应激对PFC中血糖5-HT的影响。还妊娠前的应力，但不是围产期SSRI，减少后代Cingulate皮质中的突触标志物。还围产期SSRI降低了Cingulate皮质中的糖皮质激素受体密度，特别是在雄性中。还围产期SSRIS效应被预妊娠母体压力，后代年龄和性别/性别改变。

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