Khazaei Sepideh, Jabbari Arezu, Nakhaei-Zadeh Reihaneh, Moradzadeh Morteza, Khodadadi Sayeneh, Najafi Anahita, Vaseghi Salar
Department of Psychology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Department of Physiology, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran.
Exp Brain Res. 2025 Sep 17;243(10):213. doi: 10.1007/s00221-025-07161-1.
Evidence has shown the role of brain-derived neurotrophic factor (BDNF) and glycogen synthase kinase-3 beta (GSK-3β) in the pathophysiology of posttraumatic stress disorder (PTSD). The present research explored the role of BDNF and GSK-3β activity in behavioral alterations in adolescent rats exposed to fear conditioning, extinction, and reinstatement. Three footshocks (0.8 mA for 3 s paired with sound 75 dB, 3 s) were delivered to rats. Extinction was done 1 min, or 1 h, or 1 day, or 5 days after conditioning (sound broadcasted for 20 times with no footshocks, 75 dB, 3 s). Reinstatement (one footshock, 0.8 mA, 3 s, with no sound) was done 1 h after extinction. The results showed extinction + reinstatement only in females decreased PTSD-like behaviors (darting was observed only in females). Fear conditioning decreased locomotion and rearing in both sexes, while extinction + reinstatement increased locomotion more effectively in females and rearing only in females. Fear conditioning decreased BDNF and increased GSK-3β more effectively in females, while extinction + reinstatement increased BDNF and decreased GSK-3β more effectively in females. In conclusion, we showed that BDNF and GSK-3β activity in the hippocampus may be involved in behavioral changes induced by fear conditioning and extinction + reinstatement sessions in females. However, it seems that behavioral changes in males may not be directly related to the function of BDNF and GSK-3β, although due to the absence of protein assessment, this conclusion is made with great caution. Additionally, reinstatement may induce a more powerful effect in males, counteracting the potential therapeutic effects of extinction session.
有证据表明脑源性神经营养因子（BDNF）和糖原合酶激酶-3β（GSK-3β）在创伤后应激障碍（PTSD）的病理生理学中发挥作用。本研究探讨了BDNF和GSK-3β活性在经历恐惧条件反射、消退和恢复的青春期大鼠行为改变中的作用。对大鼠施加三次足部电击（0.8 mA，持续3秒，与75分贝的声音配对，持续3秒）。在条件反射后1分钟、1小时、1天或5天进行消退训练（声音播放20次，无足部电击，75分贝，持续3秒）。在消退训练后1小时进行恢复训练（一次足部电击，0.8 mA，持续3秒，无声音）。结果显示，只有雌性大鼠的消退+恢复训练减少了PTSD样行为（仅在雌性大鼠中观察到乱窜行为）。恐惧条件反射降低了两性的运动和竖毛行为，而消退+恢复训练在雌性大鼠中更有效地增加了运动，且仅在雌性大鼠中增加了竖毛行为。恐惧条件反射在雌性大鼠中更有效地降低了BDNF并增加了GSK-3β，而消退+恢复训练在雌性大鼠中更有效地增加了BDNF并降低了GSK-3β。总之，我们表明海马体中的BDNF和GSK-3β活性可能参与了恐惧条件反射以及雌性大鼠的消退+恢复训练所诱导的行为变化。然而，雄性大鼠的行为变化似乎可能与BDNF和GSK-3β的功能没有直接关系，尽管由于缺乏蛋白质评估，得出这一结论时非常谨慎。此外，恢复训练可能在雄性大鼠中诱导出更强的效应，抵消了消退训练的潜在治疗效果。
