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内侧前额叶皮质中FKBP5的动态表达调节对条件性恐惧的恢复力。

Dynamic expression of FKBP5 in the medial prefrontal cortex regulates resiliency to conditioned fear.

作者信息

Criado-Marrero Marangelie, Morales Silva Roberto J, Velazquez Bethzaly, Hernández Anixa, Colon María, Cruz Emmanuel, Soler-Cedeño Omar, Porter James T

机构信息

Department of Basic Sciences, Ponce Research Institute, Ponce Health Sciences University, Ponce 00732, Puerto Rico.

Department of Biology, University of Puerto Rico-Ponce, Ponce 00734, Puerto Rico.

出版信息

Learn Mem. 2017 Mar 15;24(4):145-152. doi: 10.1101/lm.043000.116. Print 2017 Apr.

DOI:10.1101/lm.043000.116
PMID:28298552
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5362697/
Abstract

The factors influencing resiliency to the development of post-traumatic stress disorder (PTSD) remain to be elucidated. Clinical studies associate PTSD with polymorphisms of the FK506 binding protein 5 (FKBP5). However, it is unclear whether changes in FKBP5 expression alone could produce resiliency or susceptibility to PTSD-like symptoms. In this study, we used rats as an animal model to examine whether FKBP5 in the infralimbic (IL) or prelimbic (PL) medial prefrontal cortex regulates fear conditioning or extinction. First, we examined FKBP5 expression in IL and PL during fear conditioning or extinction. In contrast to the stable expression of FKBP5 seen in PL, FKBP5 expression in IL increased after fear conditioning and remained elevated even after extinction suggesting that IL FKBP5 levels may modulate fear conditioning or extinction. Consistent with this possibility, reducing basal FKBP5 expression via local infusion of FKBP5-shRNA into IL reduced fear conditioning. Furthermore, reducing IL FKBP5, after consolidation of the fear memory, enhanced extinction memory indicating that IL FKBP5 opposed formation of the extinction memory. Our findings demonstrate that lowering FKBP5 expression in IL is sufficient to both reduce fear acquisition and enhance extinction, and suggest that lower expression of FKBP5 in the ventral medial prefrontal cortex could contribute to resiliency to PTSD.

摘要

影响创伤后应激障碍（PTSD）发展恢复力的因素仍有待阐明。临床研究将PTSD与FK506结合蛋白5（FKBP5）的多态性联系起来。然而，尚不清楚单独的FKBP5表达变化是否会产生对PTSD样症状的恢复力或易感性。在本研究中，我们使用大鼠作为动物模型，以检查边缘下（IL）或边缘前（PL）内侧前额叶皮质中的FKBP5是否调节恐惧条件反射或消退。首先，我们在恐惧条件反射或消退过程中检查了IL和PL中的FKBP5表达。与PL中FKBP5的稳定表达相反，IL中FKBP5的表达在恐惧条件反射后增加，甚至在消退后仍保持升高，这表明IL中FKBP5的水平可能调节恐惧条件反射或消退。与此可能性一致，通过向IL局部注射FKBP5-shRNA降低基础FKBP5表达可减少恐惧条件反射。此外，在恐惧记忆巩固后降低IL FKBP5可增强消退记忆，表明IL FKBP5对抗消退记忆的形成。我们的研究结果表明，降低IL中FKBP5的表达足以减少恐惧习得并增强消退，并且表明腹内侧前额叶皮质中FKBP5的低表达可能有助于对PTSD的恢复力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37c6/5362697/16e2191694a1/Criado-MarreroLM043000f07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37c6/5362697/67ba574f3ea6/Criado-MarreroLM043000f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37c6/5362697/d9eb09843317/Criado-MarreroLM043000f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37c6/5362697/3352974abca7/Criado-MarreroLM043000f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37c6/5362697/a070de53ac80/Criado-MarreroLM043000f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37c6/5362697/17ef1aecb9a8/Criado-MarreroLM043000f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37c6/5362697/5277125fe11b/Criado-MarreroLM043000f06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37c6/5362697/16e2191694a1/Criado-MarreroLM043000f07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37c6/5362697/67ba574f3ea6/Criado-MarreroLM043000f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37c6/5362697/d9eb09843317/Criado-MarreroLM043000f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37c6/5362697/3352974abca7/Criado-MarreroLM043000f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37c6/5362697/a070de53ac80/Criado-MarreroLM043000f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37c6/5362697/17ef1aecb9a8/Criado-MarreroLM043000f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37c6/5362697/5277125fe11b/Criado-MarreroLM043000f06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37c6/5362697/16e2191694a1/Criado-MarreroLM043000f07.jpg

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