Neurobiology of Stress ( IF 4.3 ) Pub Date : 2022-11-30 , DOI: 10.1016/j.ynstr.2022.100506
Somoday Hazra 1, 2 , Joyeeta Dutta Hazra 1, 2 , Rani Amit Bar-On 3 , Yanhong Duan 4 , Shahaf Edut 1 , Xiaohua Cao 4 , Gal Richter-Levin 1, 2, 5
Traumatic stress exposure can form persistent trauma-related memories. However, only a minority of individuals develop post-traumatic stress disorder (PTSD) symptoms upon exposure. We employed a rat model of PTSD, which enables differentiating between exposed-affected and exposed-unaffected individuals. Two weeks after the end of exposure, male rats were tested behaviorally, following an exposure to a trauma reminder, identifying them as trauma 'affected' or 'unaffected.' In light of the established role of hippocampal synaptic plasticity in stress and the essential role of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in hippocampal based synaptic plasticity, we pharmacologically inhibited CaMKII or knocked-down (kd) αCaMKII (in two separate experiments) in the dorsal dentate gyrus of the hippocampus (dDG) following exposure to the same trauma paradigm. Both manipulations brought down the prevalence of 'affected' individuals in the trauma-exposed population. A day after the last behavioral test, long-term potentiation (LTP) was examined in the dDG as a measure of synaptic plasticity. Trauma exposure reduced the ability to induce LTP, whereas, contrary to expectation, αCaMKII-kd reversed this effect. Further examination revealed that reducing αCaMKII expression enables the formation of αCaMKII-independent LTP, which may enable increased resilience in the face of a traumatic experience. The current findings further emphasize the pivotal role dDG has in stress resilience.
中文翻译:
海马 CaMKII 在创伤相关精神病理学恢复中的作用
创伤性应激暴露可以形成持久的创伤相关记忆。然而,只有少数人在接触后会出现创伤后应激障碍 (PTSD) 症状。我们采用了 PTSD 大鼠模型,该模型能够区分受暴露影响的个体和未受暴露影响的个体。暴露结束两周后,在暴露于创伤提醒后,对雄性大鼠进行了行为测试,将它们识别为“受影响”或“未受影响”的创伤。鉴于海马突触可塑性在应激中的既定作用以及 Ca2+/钙调蛋白依赖性蛋白激酶 II (CaMKII) 在海马突触可塑性中的重要作用,我们在药理学上抑制 CaMKII 或敲低 (kd) αCaMKII(在两个独立的研究中)实验)在暴露于相同的创伤范例后的海马背齿状回(dDG)中。这两种操作都降低了受创伤人群中“受影响”个体的患病率。最后一次行为测试后一天,检查 dDG 中的长时程增强 (LTP),作为突触可塑性的衡量标准。创伤暴露降低了诱导 LTP 的能力,而与预期相反,αCaMKII-kd 逆转了这种效应。进一步的检查表明,减少 αCaMKII 的表达能够形成不依赖于 αCaMKII 的 LTP,这可能会增强面对创伤经历时的恢复能力。目前的研究结果进一步强调了 dDG 在抗压能力方面的关键作用。