Department of Anatomy and Neuroscience and APC Microbiome Institute, University College Cork, Cork, Ireland.
Department of Neuroscience, Icahn School of Medicine at Mount Sinai, S10-20 Hess CSM, 1470 Madison Avenue, New York, NY, 10029, USA.
Psychopharmacology (Berl). 2019 Jan;236(1):265-272. doi: 10.1007/s00213-018-5031-4. Epub 2018 Sep 13.
Post-traumatic stress disorder (PTSD) is a devastating anxiety-related disorder which develops subsequent to a severe psychologically traumatic event. Only ~ 9% of people who experience such a trauma develop PTSD. It is clear that a number of factors, including genetics, influence whether an individual will develop PTSD subsequent to a trauma. The 129S1/SvImJ (S1) inbred mouse strain displays poor fear extinction and may be useful to model this specific aspect of PTSD. The metabotropic glutamate receptor 7 (mGlu receptor) has previously been shown to be involved in cognitive processes and anxiety-like behaviour placing it in a key position to regulate fear extinction processes. We sought to compare mGlu receptor mRNA levels in the S1 strain with those in the robustly extinguishing C57BL/6J (B6) inbred strain using in situ hybridisation (ISH) in three brain regions associated with fear extinction: the amygdala, hippocampus and prefrontal cortex (PFC).
Compared to the B6 strain, S1 mice had increased mGlu receptor mRNA levels in the lateral amygdala (LA) and basolateral amygdala (BLA) subdivisions. An increase was also seen in the hippocampal CA1 and CA3 subregions of S1 mice. No difference in mGlu receptor levels were seen in the central nucleus (CeA) of the amygdala, dentate gyrus (DG) of the hippocampus or prefrontal cortex.
These data show altered mGlu receptor expression in key brain regions associated with fear extinction in two different inbred mouse strains which differ markedly in their fear extinction behaviour. Altered mGlu receptor levels may contribute to the deficit fear extinction processes seen in fear extinction in the S1 strain.
创伤后应激障碍（PTSD）是一种严重的焦虑相关障碍，发生在严重的心理创伤事件之后。只有约 9%经历过这种创伤的人会发展为 PTSD。显然，许多因素，包括遗传因素，会影响个体在经历创伤后是否会发展为 PTSD。129S1/SvImJ（S1）近交系小鼠表现出较差的恐惧消退，可能有助于模拟 PTSD 的这一特定方面。代谢型谷氨酸受体 7（mGlu 受体）先前已被证明参与认知过程和焦虑样行为，使其处于调节恐惧消退过程的关键位置。我们试图通过原位杂交（ISH）比较与恐惧消退相关的三个脑区（杏仁核、海马体和前额叶皮层（PFC））中的 mGlu 受体 mRNA 水平在 S1 品系和稳健消退的 C57BL/6J（B6）近交系之间的差异。
与 B6 品系相比，S1 小鼠的外侧杏仁核（LA）和基底外侧杏仁核（BLA）亚区的 mGlu 受体 mRNA 水平升高。S1 小鼠的海马 CA1 和 CA3 亚区也观察到增加。杏仁核中央核（CeA）、海马齿状回（DG）或前额叶皮层的 mGlu 受体水平无差异。
这些数据显示，两种不同近交系小鼠在与恐惧消退相关的关键脑区中，mGlu 受体表达发生改变，这两种近交系在恐惧消退行为上存在明显差异。mGlu 受体水平的改变可能导致 S1 品系恐惧消退中所见的恐惧消退过程缺陷。
