Regulatory Effects of Maternal Immune Activation and Environmental Enrichment on Glucocorticoid Receptor and FKBP5 Expression in Stress-sensitive Regions of the Offspring Brain.
Regulatory Effects of Maternal Immune Activation and Environmental Enrichment on Glucocorticoid Receptor and FKBP5 Expression in Stress-sensitive Regions of the Offspring Brain.
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DOI：
10.1016/j.neuroscience.2022.09.010
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发表时间：
2022-11-21
期刊：
影响因子：
3.3
通讯作者：
Hunter, Richard G.
中科院分区：
文献类型：
--
作者：
Maganga-Bakita, Ismael;Aiken, Ariel A.;Puracchio, Madeline J.;Kentner, Amanda C.;Hunter, Richard G.
众所周知，母亲在怀孕期间暴露于免疫挑战是对后代大脑发育的有害因素，也是神经精神疾病的推动力。以前的研究表明，这些不良事件可以失调的压力反应机制。被认为受到影响的应激轴的两个关键组分是这些研究中的靶点：糖皮质激素受体（GR）和调节GR活性的FKBP 5。诸如环境富集（EE）等干预措施的实施在保护大脑免受与妊娠损伤相关的后果方面显示出积极的结果。鉴于此，我们研究了GR和FKBP 5的转录调控从6个应激敏感的大脑区域的后代使用大鼠模型的母体免疫激活（MIA）。此外，我们分析了丰富的环境对他们表达的影响。我们发现MIA大鼠5个脑区的FKBP 5增加。MIA对GR的影响的RT-qPCR分析产生了不显著的结果。然而，我们发现，EE增加GR的表达在内侧视前区，这可能是一个积极的调节EE的指示。这项研究提供了证据的影响，妊娠期侮辱和EE的压力反应基因的调节在发育中的大脑。
A mother’s exposure to immune challenge during pregnancy is well known to be a detrimental factor to the development of the offspring’s brain and an impetus for neuropsychiatric disorders. Previous studies have shown that these adverse events can dysregulate the stress response machinery. Two crucial components of the stress axis considered to be affected have been targets in these studies: the glucocorticoid receptor (GR), and FKBP5 which regulates GR activity. The implementation of interventions such as Environmental Enrichment (EE) have shown positive results in protecting the brain against the consequences associated with gestational insults. In light of this, we investigated the transcriptional regulation of GR and FKBP5 from 6 stress-sensitive brain regions of the offspring using a rat model of maternal immune activation (MIA). Furthermore, we analyzed the effect of an enriched environment on their expression. We found an increase in FKBP5 in MIA rats in 5 brain regions. RT-qPCR analysis of MIA’s effect on GR yielded insignificant results. However, we found that EE increased GR expression in the medial preoptic area which could be indicative of a positive regulation by EE. This study provides evidence of the impact of both gestational insult and EE on the regulation of stress responsive genes in the developing brain.
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影响因子：
3.1
作者：
Aronoff E;Hillyer R;Leon M
通讯作者：
Leon M
影响因子：
120.7
作者：
Binder, Elisabeth B.;Bradley, Rebekah G.;Ressler, Kerry J.
通讯作者：
Ressler, Kerry J.
影响因子：
3.3
作者：
Donatti, Teresinha Lermen;Koch, Vera Hermina Kalika;Pereira, Rosa Maria Rodrigues
通讯作者：
Pereira, Rosa Maria Rodrigues
早期压力作为酒精和药物依赖性的预测因素。
影响因子：
3.4
作者：
Enoch, Mary-Anne
通讯作者：
Enoch, Mary-Anne
影响因子：
2
作者：
Criado-Marrero, Marangelie;Silva, Roberto J. Morales;Porter, James T.
通讯作者：
Porter, James T.