Aykac Asli, Şehirli Ahmet Özer, Gören M Zafer
Department of Biophysics, Faculty of Medicine, Near East University, Near East University Boulevard, 99138, Nicosia, Cyprus.
Bioinformatics and Computational Research Group, DESAM Institute, Near East University, Boulevard, 99138, Nicosia, Cyprus.
J Mol Neurosci. 2020 Jul;70(7):1120-1129. doi: 10.1007/s12031-020-01518-7. Epub 2020 Mar 4.
The predator scent-induced (PSI) stress model is a rat model used to mimic post-traumatic stress disorder (PTSD) symptoms in humans. There is growing evidence that prazosin, which blocks α-1 and is approved by the FDA as an anti-hypertensive drug, can potentially be of use in the treatment of PTSD-related sleep disorders. The aim of this study was to investigate the role of prazosin treatment on behavioral parameters (freezing time, total transitions, and rearing frequency measured from the open field; anxiety index, total entries and time spent in open arms calculated from the elevated plus maze), apoptotic proteins and α-2c-AR in fear memory reconsolidation in the PSI stress rat model. We used western blot analysis to determine the effect of prazosin (0.5 mg/kg/ip) on α-2c-AR and apoptotic protein expression changes in the frontal cortex, hippocampus, and amygdala. It was determined that in the stress group, there was increased freezing time and anxiety index, and decreased rearing frequency, total transitions, total entries, and time spent in open arms compared to the control groups. Following PSI-stress, pro-apoptotic (bax) protein expression levels increased and α-2c AR and anti-apoptotic protein (bcl-2) levels decreased in investigated all brain regions. The majority of stress-induced changes were recovered with prazosin treatment. The results of our study may potentially be useful in understanding the effect of prazosin treatment, given the fact that the amygdala, frontal cortex, and hippocampus regions are affected for stress conditions.
捕食者气味诱导(PSI)应激模型是一种用于模拟人类创伤后应激障碍(PTSD)症状的大鼠模型。越来越多的证据表明,可阻断α-1且已获美国食品药品监督管理局(FDA)批准作为抗高血压药物的哌唑嗪,可能可用于治疗与PTSD相关的睡眠障碍。本研究的目的是调查哌唑嗪治疗对PSI应激大鼠模型恐惧记忆再巩固中行为参数(旷场试验测得的僵住时间、总转换次数和直立频率;高架十字迷宫计算出的焦虑指数、进入开放臂的总次数和在开放臂中花费的时间)、凋亡蛋白和α-2c-肾上腺素能受体(α-2c-AR)的作用。我们采用蛋白质免疫印迹分析来确定哌唑嗪(0.5mg/kg腹腔注射)对额叶皮质、海马体和杏仁核中α-2c-AR及凋亡蛋白表达变化的影响。结果发现,与对照组相比,应激组的僵住时间和焦虑指数增加,而直立频率、总转换次数、进入开放臂的总次数和在开放臂中花费的时间减少。在PSI应激后,所有被研究脑区中促凋亡蛋白(bax)的表达水平升高,而α-2c AR和抗凋亡蛋白(bcl-2)的水平降低。大多数应激诱导的变化在哌唑嗪治疗后得到恢复。鉴于杏仁核、额叶皮质和海马体区域在应激状态下会受到影响,我们的研究结果可能有助于理解哌唑嗪治疗的效果。