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miR-132 Regulates PTSD-like Behaviors in Rats Following Single-Prolonged Stress Through Fragile X-Related Protein 1.
Cellular and Molecular Neurobiology ( IF 4 ) Pub Date : 2020-04-24 , DOI: 10.1007/s10571-020-00854-x
Peng-Yin Nie 1 , Li-Li Ji 1 , Chang-Hai Fu 1 , Jun-Bo Peng 1 , Zhen-Yu Wang 1 , Lei Tong 1
Affiliation  

Fragile X-related protein 1 (FXR1) is a member of the fragile X family of RNA-binding proteins, which regulates a number of neurological and neuropsychiatric disorders such as fragile X syndrome, and is expected as a novel therapeutic target for some psychiatric diseases. However, it is unknown how FXR1 changes and functions in post-traumatic stress disorder (PTSD), a common mental disorder related to trauma and stressor. In this study, we characterized the expression pattern of FXR1 in the pathophysiological process of PTSD and further investigated the possible mechanism underlying these changes by finding an upstream regulator, namely miRNA-132 (miR-132). Furthermore, we verified whether miR-132 silence had an effect on the PTSD-like behaviors of single prolonged stress (SPS) rats through open field test, forced swimming test, and water maze test. At last, we examined the expression levels of PSD95 and synapsin I in the hippocampus, which was one of the key brain regions associated with PTSD. We showed that the levels of FXR1 and fragile X mental retardation protein (FMRP), an autosomal homolog of FXR1, were decreased in the hippocampus of PTSD rats, but the levels of PSD95 and synapsin I were increased, which could be reversed by downregulation of miR-132. The results revealed that miR-132 could modulate PTSD-like behaviors in rats following SPS through regulating FXR1 and FMRP.

中文翻译:

miR-132 通过脆性 X 相关蛋白 1 调节大鼠在单一长期应激后的 PTSD 样行为。

脆性 X 相关蛋白 1 (FXR1) 是脆性 X 家族 RNA 结合蛋白的成员,可调节多种神经和神经精神疾病,如脆性 X 综合征,有望成为某些精神疾病的新治疗靶点. 然而,尚不清楚 FXR1 在创伤后应激障碍 (PTSD) 中如何变化和发挥作用,这是一种与创伤和压力源相关的常见精神障碍。在这项研究中,我们表征了 FXR1 在 PTSD 病理生理过程中的表达模式,并通过寻找上游调节因子,即 miRNA-132 (miR-132) 进一步研究了这些变化的可能机制。此外,我们通过旷场试验、强迫游泳试验、和水迷宫测试。最后,我们检查了海马体中 PSD95 和突触素 I 的表达水平,海马体是与 PTSD 相关的关键大脑区域之一。我们发现 PTSD 大鼠海马中 FXR1 和脆性 X 智力低下蛋白 (FMRP)(FXR1 的常染色体同源物)的水平降低,但 PSD95 和突触素 I 的水平升高,这可以通过下调miR-132。结果表明,miR-132 可以通过调节 FXR1 和 FMRP 来调节 SPS 后大鼠的 PTSD 样行为。PTSD 大鼠海马体中 PSD95 和突触素 I 水平升高,这可以通过下调 miR-132 来逆转。结果表明,miR-132 可以通过调节 FXR1 和 FMRP 来调节 SPS 后大鼠的 PTSD 样行为。PTSD 大鼠海马体中 PSD95 和突触素 I 水平升高,这可以通过下调 miR-132 来逆转。结果表明,miR-132 可以通过调节 FXR1 和 FMRP 来调节 SPS 后大鼠的 PTSD 样行为。
更新日期:2020-04-24
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