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The Impact of FKBP5 Deficiency in Glucocorticoid Receptor Mediated Regulation of Synaptic Transmission in the Medial Prefrontal Cortex
Neuroscience ( IF 3.3 ) Pub Date : 2020-12-25 , DOI: 10.1016/j.neuroscience.2020.12.020
Hakyun Ryu 1 , Myunghyun Cheon 1 , ChiHye Chung 1
Affiliation  

Exposure to stress activates glucocorticoid receptors in the brain and facilitates the onset of multitude psychiatric disorders. It has been shown that FK506 binding protein 51 (FKBP5) expression increases during glucocorticoid receptor (GR) activation in various brain regions including the medial prefrontal cortex (mPFC). FKBP5 knockout (KO) mice are reported to be resilient to stress, however, it remains uninvestigated whether FKBP5 loss affects neurotransmission and if so, what the functional consequences are. Here, we examined the impact of FKBP5 deletion in synaptic transmission of the mPFC. We found that GR activation significantly decreased excitatory neurotransmission in the mPFC, which was completely abolished upon FKBP5 deletion, in consistent with behavioral resilience observed in FKBP5 KO mice. Even though FKBP5 loss has minimal impact on neural excitability, we found that FKBP5 deletion distorts the excitatory/inhibitory balance in the mPFC. Our study suggests that FKBP5 deficiency leads to the mPFC insensitive to GR activation and provides a neurophysiological explanation for how FKBP5 deficiency may mediate stress resilience.



中文翻译:

FKBP5缺乏对糖皮质激素受体介导的内侧前额叶突触传递调节的影响

暴露于压力会激活大脑中的糖皮质激素受体并促进多种精神疾病的发作。已经表明,FK506 结合蛋白 51 (FKBP5) 的表达在包括内侧前额叶皮层 (mPFC) 在内的各个大脑区域的糖皮质激素受体 (GR) 激活期间增加。据报道,FKBP5 敲除 (KO) 小鼠对压力具有弹性,但是,FKBP5 缺失是否会影响神经传递以及如果是,功能后果是什么仍未研究。在这里,我们检查了 FKBP5 缺失对 mPFC 突触传递的影响。我们发现 GR 激活显着降低了 mPFC 中的兴奋性神经传递,这在 FKBP5 缺失后完全消失,与在 FKBP5 KO 小鼠中观察到的行为恢复一致。尽管 FKBP5 丢失对神经兴奋性的影响很小,但我们发现 FKBP5 缺失会扭曲 mPFC 中的兴奋/抑制平衡。我们的研究表明,FKBP5 缺乏导致 mPFC 对 GR 激活不敏感,并为 FKBP5 缺乏如何介导压力恢复提供了神经生理学解释。

更新日期:2021-01-28
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